The Latest and Greatest in Insulin Pumps and Sensor Technology

diabetes pumps and sensors

love pumps and sensors!

As a certified diabetes educator (or as I prefer to say, type 1 coach), I have started literally hundreds of patients on insulin pumps over the last few decades. I have a disclaimer: I do not wear a pump and do not have type 1 diabetes. But I have worked in the field from clinics to ski and summer camps, as a dog sled driver for little munchkins with our team of sled dogs, to backpacking and canoe trips – all with people who do have type 1 diabetes. Sometimes I grunt and groan when I get up to start an adventure, but then I meet up with the group and see someone taking shots! My emotions turn to glee when someone has a pump and a sensor…I realize it sometimes feels like being the bionic man or woman with all this technology but hey, what’s wrong with being such a diabetes stud or studdette?

So what is so cool about pump and sensor technology?

Well, if you’re like me and you like to participate in group sports or activities, the technology is amazing. Let’s say you are just starting off on an adventure (whatever that may be) with a group and you note on your sensor that your blood glucose (BG) is 50 mg/dL.


Who wants to stop the whole team from proceeding? But then you realize you can take in some carbohydrates, lower your basal rate temporarily, and watch your sensor to see if you are coming up and are not only good to go, but where you will be in 5, 10, 15, 20 minutes…you get the idea.

What are the options available right now to help you manage your diabetes?

The Omnipod insulin pump is the only full functioning patch pump, meaning it is programmable with insulin-to-carb ratios, target BG, correction factors, etc. so your math is done for you. At this time, the Omnipod pump does not integrate with a sensor but you can certainly use the Dexcom sensor independently.

There are also two patch pumps that are not programmable and have a bolus only option (OneTouch Via) and basal/bolus option (V-Go). These are more likely options for those with type 2 diabetes.

The Tandem insulin pump does have a tube that most folks find a minor inconvenience. Its great new claim to fame is that, as the software is updated (and technology is changing so fast!), you can update your pump via the cloud. How cool is that! Your pump does not get outdated since the pump software is updated. This includes future changes, such as Dexcom sensor data on the screen, auto-suspend as needed with hypoglycemia, and the eventual goal of a fully integrated sensor and pump where the pump responds to the data from the sensor and alters insulin delivery.

tandem and dexcom cgm

The Medtronic insulin pump company has led the charge not only with a sensor integrated pump where the sensor data is seen on the pump screen, but where the pump responds to low blood glucose values and impending lows, and adjusts basal rates as needed based on your basal history. Be warned, this is not a cure and still requires diligence on your part or the system will fail. Fasting blood glucose values have been shown to be excellent – generally close to the pump set target range of 120 mg/dL.

MiniMed 670G

You can always choose to continue with injections and utilize one of two sensors. Dexcom (glucose readings every 5 minutes on a receiver or your cell phone) or the new Freestyle Libre that allows you to scan your sensor patch and see your glucose on a receiver.

And where is all of this going?

Oh – it is so exciting! I am confident that in the next five years a fully automated system will be available with minimal input from the user. Tandem, Omnipod and Medtronic are all working on fully integrated pumps as responsibly fast as they can. In addition, other options are coming too, including a dual hormone system that has reservoirs for insulin and glucagon to keep you safe. And with the new insulin from Novo Nordisk that is reputed to start absorption in 2.5 minutes (wow!) one of the big barriers to insulin delivery may have just been resolved.

Although a cure is what we are all hoping for, technology is the next best thing.

Embrace it and stay tuned!

Automated Insulin Delivery (Artificial Pancreas, Closed Loop)

artifiical pancreas


The development of automated insulin delivery has many names – artificial pancreas, hybrid closed loop, Bionic Pancreas, predictive low glucose suspend – but all share the same goal: using continuous glucose monitors (CGMs) and smart algorithms that decide how much insulin to deliver via pump. The goal of these products is to reduce/eliminate hypoglycemia, improve time-in-range, and reduce hyperglycemia – especially overnight.

See below for an overview of the automated insulin delivery field, focused on companies working to get products approved. Do-it-yourself automated insulin delivery systems like OpenAPS and Loop are not included here, though they are currently available and used by a growing number of motivated, curious users.

We’ve also included helpful links to articles on specific product and research updates, as well as some key questions.

Who is Closing the Loop and How Fast Are They Moving?

Below we include a list of organizations working to bring automated insulin delivery products to market – this includes their most recently announced public plans for pivotal studies, FDA submissions, and commercial launch. The organizations are ordered from shortest to longest time to a pivotal study, though these are subject to change. This list excludes those without a commercial path to market (e.g., academic groups). The first table focuses on the US, with European-only systems listed in the second table.

Updated: November 4, 2017

US Products

Company / Organization Product Latest Timing in the US
Medtronic MiniMed 670G/Guardian Sensor 3 – hybrid closed loop that automates basal insulin delivery (still requires meal boluses) FDA-approved and currently launching this fall to ~35,000 Priority Access Program participants in the US. Pump shipments to non-Priority Access customers will start in October, with sensors and transmitters to ship by the end of 2017 or early 2018. Medtronic is experiencing a global CGM sensor shortage that won’t resolve until spring 2018.
Tandem t:slim X2 pump with built-in predictive low glucose suspend (PLGS) algorithm; Dexcom G5 CGM

t:slim X2 pump with built-in Hypoglycemia-Hyperglycemia Minimizer algorithm; Dexcom G6 CGM (including automatic correction boluses)

Launch expected in summer 2018. Pivotal trial now underway, with FDA submission expected in early 2018.

Launch expected in the first half of 2019. Pivotal trial to begin in the first half of 2018.

Insulet OmniPod Horizon: pod with built-in Bluetooth and embedded hybrid closed loop algorithm, Dash touchscreen handheld, and Dexcom G6 CGM

User will remain in closed loop even when Dash handheld is out of range

Launch by end of 2019 or early 2020, with a pivotal study in 2018
Bigfoot Biomedical Smartphone app, insulin pump (acquired from Asante), and a next-gen version of Abbott’s FreeStyle Libre CGM sensor (continuous communication)

The smartphone is expected to serve as the window to the system and complete user interface

Launch possible in 2020, with a pivotal trial expected in 2018
Beta Bionics Bionic Pancreas iLet device: dual chambered pump with built-in algorithm; hybrid or fully closed loop; insulin-only or insulin+glucagon; custom infusion set, Dexcom CGM

Likely to launch as insulin-only product, with glucagon to be optionally added later

Currently using Zealand’s pumpable glucagon analog

Insulin-only: possible US launch in the first half of 2020, with a pivotal trial to start in the beginning of 2019.

Insulin+glucagon (bihormonal) pivotal trial expected to start in the beginning of 2019. Timing of FDA submission and launch depend on a stable glucagon, among other things.

European Products

Company / Organization Product Latest Timing in Europe
Medtronic MiniMed 640G/Enlite Enhanced – predictive low glucose management

MiniMed 670G/Guardian Sensor 3 – hybrid closed loop that automates basal insulin delivery (still requires meal boluses)

Currently available in Europe

No timing recently shared. Approval was previously expected in summer 2017

Diabeloop Diabeloop algorithm running on a wireless handheld, Cellnovo patch pump, Dexcom CGM Pivotal trial expected to complete in February/March 2018. Possible European launch in 2018
Roche, Sensonics, TypeZero Will use Senseonics’ 180-day CGM sensor, Roche pump and TypeZero algorithm Pivotal trial expected to begin in Europe in early 2018
Cellnovo, TypeZero Cellnovo patch pump with integrated TypeZero algorithm; presumably a Dexcom CGM Aims for a 2018 European launch. No pivotal trial details shared

Helpful Links

Medtronic: MiniMed 670G




Beta Bionics

Test Drives:

test drive – UVA’s Overnight Closed-Loop Makes for Great Dreams. Kelly participates in UVA’s overnight closed loop trial and reports back on an incredible opportunity for the field to move fast, reduce anxiety, and beat timelines.

test drive – Kelly and Adam take UVA’s DiAs artificial pancreas system home 24/7 for a three-month study. Their key takeaways, surprises, and next steps.

Key Questions for the Artificial Pancreas

Are patient expectations too high? If we expect too much out of first-generation artificial pancreas systems – e.g., “I don’t have to do anything to get a 6.5% A1c with no hypoglycemia” – we might be disappointed. Like any new product, early versions of the artificial pancreas are going to have their glitches and shortcomings. Undoubtedly, things will improve markedly over time as algorithms advance, devices get more accurate and smaller, insulin gets faster, infusion sets improve, and we all get more experience with automated insulin delivery. But it takes patience and persistence to weather the early generations to get to the truly breakthrough products. We would not have today’s small insulin pumps without the first backpack-sized insulin pump; we would not have today’s CGM without the Dexcom STS, Medtronic Gold, and GlucoWatch; we would not be walking around with smartphones were it not for the first brick-sized cellphones. Our research trial experience with automated insulin delivery recalibrated our expectations a bit – these systems are going to be an absolutely terrific advance for many patients, but they will not replace everything out of the gate. Let’s all remember that devices need to walk first, then run, and it’s okay if the first systems are more conservative from a safety perspective.

What fraction of patients will be willing to wear some type of automated insulin delivery system? Right now, many estimate that ~30% of US type 1’s wear a pump, and about 15% to 20% wear CGM. There are a lot of reasons why that may be the case, including cost, hassle, no perceived benefit, no desire to switch from current therapy, wearing a device on the body, alarm fatigue, etc. Will automated insulin delivery address enough of these challenges to expand the market?

Will healthcare providers embrace automated insulin delivery? Today, healthcare providers lose money when they prescribe pumps and CGM – they are very time consuming to train, prescribe, and obtain reimbursement for. We need to make sure that automated insulin delivery systems make providers’ lives easier, not more complicated.

Will there be a thriving commercial environment and reimbursement? It’s extremely expensive to develop and test closed-loop systems, and companies will only develop them if there is a commercial environment that supports a reasonable business. Reimbursement is a major part of that, and it’s hard to know if insurance companies will pay for closed-loop systems for a wide population of patients. We are optimistic that reimbursement will be there, especially if systems can simultaneously lower A1c, reduce hypoglycemia, and improve time-in-range.

What’s the right balance between automation and human manual input? The holy grail is a fully-automated, reactive closed loop that requires no meal or exercise input. But insulin needs to get faster to make that a reality. For now, daytime systems need to deal with balancing human input with automation, and there’s an associated patient learning curve. How much should automated insulin delivery systems ask patients to do? How do we ensure patients do not forget how to manage their diabetes (“de-skilling”) as systems grow in their automation abilities?

Insulin-only or insulin+glucagon? Ultimately, we believe that the question is partially one of patient preferences. There will be some patients who may want the extra glycemic control offered by the dual-hormone approach and will be willing to accept a bit more risk or a more aggressive algorithm. An insulin+glucagon system could be helpful for those with hypoglycemia unawareness, and if such a system makes it to the market, some patients will certainly want to give it a try. We believe a range of options is a good thing for people with diabetes, since all systems and products have pros and cons. Ultimately, cost considerations may present the largest factor in adoption. An insulin+glucagon system certainly brings multiple cost elements to consider – a second hormone, a dual-chambered pump, custom infusion sets, potentially higher training, etc. It’s hard to know at this point how the relative costs/benefits will exactly compare to insulin-only systems.

Drugs with dual-hormone action gain attention in diabetes field.

Engineered peptide drugs that simultaneously target two hormone receptors have historically attracted interest among scientists hoping to create new treatments for diabetes. Now, many in the field seem buoyed by new data from a class of diabetes medicines designed to mimic gastrointestinal hormones called incretins, which stimulate insulin release from pancreatic beta cells.

The ‘incretin mimetics’ currently on the market modulate only one receptor. For example, Byetta (exenatide) from California’s Amylin Pharmaceuticals and Victoza (liraglutide) from Denmark’s Novo Nordisk trigger the glucagon-like peptide-1 receptor (GLP-1). To adequately control blood glucose, these drugs are often used at high doses, commonly causing vomiting and nausea. Long-term effects could include increased risk for pancreatitis, pancreatic cancer and thyroid cancer.

The problem is that GLP-1 receptors aren’t confined just to the gut. They’re also found in other tissues, especially the thyroid, pancreas, meninges, kidney and bone. In March, the US Food and Drug Administration began reviewing research linking GLP-1 agonists to increased risk of pancreatitis and precancerous cellular changes associated with pancreatic cancer. And this September, France’s Sanofi withdrew a new drug application in the US for its once-daily injectable GLP-1 agonist lixisenatide owing to concerns over cardiovascular safety.

According to drug developers, drugs that target two receptors simultaneously could provide a solution by more closely approximating the normal physiology lost when type 2 diabetes develops. The hope is to use these drugs at lower doses, decreasing the likelihood for adverse reactions.

Jim Dowdalls / Science Source

Dual fuel: Two-hormone drugs help treat diabetes.

In addition to GLP-1, another endogenous gut hormone is glucose-dependent insulinotropic peptide (GIP), which stimulates postprandial insulin release. Activity of GLP-1 and GIP is thought by some to be impaired in type 2 diabetes. A paper published in late October detailed the effects in humans of a new compound—originally called MAR701 by Indiana’s Marcadia Biotech, which contributed to early development of the compound—that binds and triggers receptors for both GLP-1 and GIP1. It offered data from a phase 2 trial done in collaboration with Roche, the Swiss drug giant, that included 53 patients with inadequately controlled type 2 diabetes.

The trial found a dose-dependent decrease in hemoglobin A1C (HbA1c) in the experimental group, ranging from a decrease of 0.53% to as much as a 1.11% drop; by comparison, the placebo group had an average drop of 0.16%. No participants experienced vomiting, a common side effect of incretin mimetics on the market, and few had nausea. The study also reported that this type of dual agonist lowers blood glucose levels and weight more effectively than single agonists in animal models.

Incredible incretin?

According to study author Matthias Tschöp, scientific director of the Helmholtz Diabetes Center in Munich, the pace of research on engineered peptides for dual-agonist incretin-based therapy has picked up in recent years. Tschöp and his collaborator Richard DiMarchi, a chemist at the University of Indiana in Bloomington, have worked previously on a GLP-1 and glucagon receptor co-agonist, in collaboration with New Jersey–based Merck, and a GLP-1 and estrogen receptor co-agonist, the latter of which showed potential for reversing the metabolic syndrome in rodents2.

Other researchers are in hot pursuit of similar drugs. Scientists at Amylin Pharmaceuticals, which was acquired last year by New York’s Bristol-Myers Squibb, are working on peptide hybrids made of an analog of Byetta linked to davalintide, which mimics amylin, a hormone released from pancreatic beta cells that helps regulate blood glucose levels after a meal3. “The exendin-amylin mimetic peptide hybrids . . . improve glucose tolerance and reduce HbA1c levels in diabetic rodents, coupled with body weight loss that is greater than that achieved by the parent peptides,” says Soumitra Ghosh, senior director of research programs and collaborations at Amylin.

Researchers at the University of Copenhagen and the University of Alberta, in Canada, in collaboration with Denmark’s Zealand Pharma and Germany’s Boehringer Ingelheim, are working on a single molecule that mimics the gut hormone oxyntmodulin, an endogenous peptide hormone with dual GLP-1 and glucagon receptor agonist activity4. The team is in competition with Merck, which has explored oxyntmodulin mimetics, including one called DualAg5.

Some teams are even looking into triple-receptor agonists. Nigel Irwin, a pharmacologist at the Diabetes Research Group at the University of Ulster in Ireland, works with a group focused on preclinical drug discovery of novel peptides for treating metabolic disease and obesity. Irwin’s team published results in late October showing that a hybrid triple agonist, combining the effects of GLP-1, GIP and glucagon, decreased body weight and significantly improved glucose tolerance and insulin sensitivity in mice fed high-fat diets, as compared to conventional antidiabetic agents6. “We also believe that concurrent activation of three receptors will minimize any potential side effects that can occur through over stimulation of a single regulatory peptide receptor,” Irwin explains.


Noninjectable Insulin Developers Make Progress

Diabetes sufferers may soon be able to avoid the needle.

Noninjectable Insulin Developers Make ProgressLessons from past failures are being applied by drug developers pursuing clinical development of new oral and inhalable insulin products. [AndrzejTokarski/Fotolia]

Whether famous like Tom Hanks or not, millions of people with diabetes for generations have had to take insulin by injection, just as a 14-year-old diabetic named Leonard Thompson did when he became the first patient successfully treated with the peptide hormone in 1922.

Nearly a century later, drug developers remain unable to market a noninjectable therapeutic. But of late, lessons from past failures are being applied by drug developers pursuing clinical development of new oral and inhalable insulin products. The companies see a growing market: An estimated 552 million people are expected to develop diabetes by 2030, up from 371 million in 2012, according to the International Diabetes Federation.

No Needles Required

MannKind earlier this month resubmitted to FDA its new drug application for Afrezza® (insulin human [rDNA origin]) Inhalation Powder for adults with type 1 or type 2 diabetes)—two years after the agency required two additional clinical studies comparing its current inhaler to its first-generation MedTone inhaler.

In August, MannKind released promising results from two Phase III trials. One study in type 1 patients compared Afrezza to insulin aspart; the other measured inhalable insulin in type 2 patients with inadequate diabetes control following metformin treatment, with or without a second or third oral medication. The type 2 study showed a drop in mean A1c levels of 0.82% in patients using Afrezza, compared to a 0.42% decrease in the comparator group. The type 1 study met its primary endpoint of noninferiority to insulin aspart.

Afrezza combines an inhalation powder with an inhaler called Dreamboat™ designed for use by diabetics at the start of meals. The powder dissolves immediately when inhaled to the deep lung and delivers insulin quickly to the bloodstream. According to MannKind, peak insulin levels occur within 12 to 15 minutes of administration, compared with 45 to 90 minutes for injected rapid acting insulin analogs, and 90–150 minutes for injected regular human insulin.

Joseph Kocinsky, MannKind’s svp, pharmaceutical technology development, told GEN Afrezza’s Technosphere® pulmonary drug delivery platform offers competitive advantages. In addition to ultra-fast delivery, insulin administered via Technosphere formulation avoids the hepatic first-pass metabolism that reduces drug bioavailability.

“The Technosphere technology is applicable to a wide variety of drugs (small molecules, peptides, proteins, monoclonal antibodies) and a wide variety of clinical indications like diabetes, pain, osteoporosis, and respiratory disease,” Kocinsky said.

Perhaps Afrezza’s best advantage is the same one offered by the oral insulin products—it doesn’t require a needle. Injection remains no small hurdle to insulin use among people with diabetes, despite improvements over the past generation such as shorter and sharper disposable needles, notes Robert E. Ratner, M.D., FACP, FACE, chief scientific and medical officer for the American Diabetes Association.

Dr. Ratner’s previously work as an investigator included studying Novo Nordisk’s insulin degludec, a long-acting injectable insulin analog. He said injection has one important advantage: Doses can be titrated and adjusted.

“When you’re giving oral or inhaled insulin, that level of precision in terms of dosing is probably going to be considerably harder,” Dr. Ratner told GEN. “We don’t yet know all of the details about the pharmacokinetics of these [noninjectable] agents—how quickly they’ll get absorbed, what percentage will get absorbed, are we going to be able to change the doses to meet the biologic needs of the individual? Those all remain unknowns. Those are the hurdles the companies need to overcome before we have a viable product.”

Road to Success Paved with Failure

Drug developers have long struggled to develop noninjectable diabetes treatments. In 2007, Pfizer stopped marketing Exubera® after 13 months following disappointing sales, took $2.8 billion in pre-tax charges, and returned product rights to partner Nektar Therapeutics.

One key factor in Exubera’s failure was its delivery system: Its inhaler was about a foot long, more conspicuous and clumsier than even the needle. Afrezza can be inhaled through a smaller inhaler requiring no maintenance because it is discarded and replaced every 15 days. Also unlike Exubera, Afrezza is dosed in traditional insulin units that are linear; two three-unit cartridges equal a six-unit cartridge.

Within months of Exubera’s exit, both Novo Nordisk and Eli Lilly ended programs to develop new inhalable insulin products that had advanced to Phase III trials, insisting they had not acted from safety concerns. Lilly brought insulin to market in 1923, and 60 years later launched the first insulin analogs.

Today, Novo Nordisk and another drug developer, Oramed, are well into clinical studies of oral insulin products, with years to go: “We won’t be looking at oral insulin for the next five to six years at the very least.”

Future Possibilities

Also working on noninjectable insulin is Biocon, which last year landed Bristol-Myers Squibb (BMS) as its partner to partially fund Phase II trials of its IN-105 outside India for two years. After that, BMS has the option to assume full responsibility for IN-105, including all development and commercialization activities outside India—in return for BMS paying Biocon a license fee, milestone payments, and royalties on IN-105 sales outside India.

Oramed in July enrolled its first patient in a Phase IIa trial assessing the safety of ORMD-0801, an orally ingestible insulin capsule on patients with type 2 diabetes. A total 30 patients will be enrolled.

“Results of the trial are anticipated by the end of the calendar year,” Aviva Sherman, an Oramed spokeswoman, told GEN.

ORMD-0801 is also under study in a clinical trial in Israel in August that began recruiting patients with type 1 diabetes, for which -0801 is envisioned as a complement to injections, allowing fewer daily injections.

In September, Oramed submitted a pre-IND package to FDA for its ORMD-0901 (oral exenatide), a GLP-1 analog for type 2 diabetes. “By acting on multiple fronts, i.e., stimulation of insulin release and suppression of glucagon release, as well as other actions, GLP-1 addresses diabetes-related glycemia issues on a broader level than does exogenously administered insulin,” Sherman said.

Oramed said its oral insulin mimics insulin’s natural location and gradients in the body by traveling through the gastrointestinal tract encapsulated, then releasing the insulin in the small intestine, from which it is ferried to the liver via the portal vein. The first-pass metabolism significantly reduces the risk of hypoglycemia, the most common side effect of injected insulins.

Novo Nordisk’s candidate OI362GT or NN1954, an oral basal insulin analog intended as a tablet treatment, generated successful results from a single-dose Phase I trial earlier this year. Peter Kurtzhals, svp in diabetes research at Novo Nordisk, told GEN NN1954 is delivered through enteric coated tablets targeting the duodenum, facilitated by the rise in pH that occurs when a substance passes from the acidic milieu in the stomach into the intestine.

“The delivery in duodenum is not more porous, but contents of the gall fluid secreted here may play a role in facilitating absorption of some substances from this part of the gut,” Kurtzhals said.

NN1954 absorption is enabled via partner Merrion Pharmaceuticals’ GIPET® technology. GIPET uses specifically designed oral formulations of patented absorption enhancers designed to activate micelle formation, facilitating transport of drug and increasing absorption.

The drug and enhancer are not bound to each other chemically, but are both ingredients of the tablet, with no interaction between active pharmaceutical ingredient and absorption enhancer. Co-release of the drug and absorption enhancer occurs following dissolution of the coating and a general disintegration of the tablet.

“The oral insulin project is currently in Phase I clinical development. Contingent on successful outcome of these trials, Phase II will be initiated within 1–2 years,” Kurtzhals said.

By the time Novo Nordisk and Oramed complete their required additional trials, followed by formal regulatory reviews, MannKind may have already delivered the first noninjectable insulin to grateful diabetics. Or not. FDA can be expected to show particular caution with noninjectable insulin candidates, given the problems inhalables have had in recent years. To win approvals, companies will have to show not only the usual safety and efficacy, but that their products are better than past noninjectable candidates—drugs young Leonard Thompson could only dream about when he took insulin by needle and made history nearly a century ago.

Liraglutide-metformin combo superior to either treatment alone for weight loss in PCOS.

Short-term combination liraglutide and metformin yielded significant weight loss among obese women with polycystic ovary syndrome,Mojca Jensterle Sever, MD, PhD, of the University Medical Center in Ljubljana, Slovenia, told Endocrine Today here at ENDO 2013.

Obesity is a great problem in women with polycystic ovary syndrome (PCOS) and we do not have a conventional satisfactory treatment for it. The most widely used drug is metformin for women with PCOS and metabolic disturbances, but it’s somehow not successful enough to curb obesity. That’s why we tried to use our experience with diabetes to test long-acting GLP-1 agonists for any effect on the PCOS population,” Jenterle Sever said in an interview.

She and colleagues conducted a 12-week open, metformin-controlled trial by randomly assigning 36 obese women with PCOS aged 31.3 years (BMI 37.1 kg/m2) to one of the following treatment arms: metformin 1,000 mg twice daily (n=14), liraglutide (Victoza, Novo Nordisk) 1.2-mg administered daily subcutaneously (n=11) or combined therapy (n=11).

Jensterle Sever said that 38% of patients lost ≥5% body weight (22% in the combination group, 16% in the liraglutide group and zero in the metformin group). Patients assigned to combination therapy lost an average of 6.5 kg vs. 3.8 kg among those in the liraglutide group and 1.2 kg in the metformin group (P<.001), according to data.

Patients in the combination group also demonstrated a greater decrease in BMI and waist circumference compared with the other two treatment groups, according to data.

“We found that this combined arm was more successful in reducing weight, BMI and waist circumference as compared with liraglutide and metformin treatment arm alone.”

Adverse events included nausea during liraglutide treatment. However, this effect gradually declined over time and was not correlated with weight loss, Jensterle Sever said.

These findings suggest that short-term combined treatment of liraglutide and metformin led to statistically significant weight loss in obese women with PCOS. – by Samantha Costa

Source: Endocrine today

Has pancreatic damage from glucagon suppressing diabetes drugs been underplayed?.

Incretin mimetics have been called “the darlings of diabetes treatment” and they may soon also be licensed for treating obesity. But a BMJ investigation has found growing safety concerns linked to the drugs’ mechanism of action. Deborah Cohen asks why patients and doctors have not been told.

They’ve been touted as the “new darlings of diabetes treatment”—the biggest breakthrough since the discovery of insulin nearly a hundred years before. The so called incretin therapies—glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors—looked as if they might change the face of type 2 diabetes. Their dual action of switching on insulin and suppressing glucagon to help control blood glucose was the ultimate in diabetes care.

The promise of a Nobel prize for the investigators loomed large. Scientists had discovered a treatment that could potentially modify disease progression. Studies in experimental animals showed that GLP-1 caused a proliferation in new insulin producing β cells. The hope was that these new cells might be able to replace those that died off in the course of human diabetes.

Nor did the promise end there. GLP-1 acts on the brain to makes people feel less hungry and the more powerful drugs aid weight loss—rather than weight gain like many antidiabetic drugs before them.

It’s an effect companies are seeking to market in its own right. Spurred on by the US Food and Drug Administration’s willingness to license new obesity treatment, Novo Nordisk’s chief science officer Mads Krogsgaard Thomsen said last year that the “political establishment in the US now knows that behaviour change alone is not enough.”1

His company’s drug, liraglutide, is in the process of late stage clinical tests, which Thomsen says show promising results.

But an investigation by the BMJ suggests Thomsen’s confidence might be optimistic. Concerns held by some specialists about the potential side effects of GLP-1 drugs have emerged into the mainstream after both the FDA and the European Medicines Agency announced in March that they would launch a review into whether the drugs may cause or contribute to the development of pancreatic cancer.

As yet neither agency has reached any conclusions, but they are meeting to discuss the matter later this month. And, as this investigation has found, for the regulators it is not a new concern. Over the years, drug assessors have become increasingly concerned that the incretin drugs have the potential for unwanted proliferative effects.

Expert concerns

Concerns long held by some experts about the potential side effects of incretin mimetics have gathered momentum with three publications this year. An independent analysis of health insurance data published in February found that people taking exenatide and sitagliptin were at twice the risk of hospital admission for acute pancreatitis compared with people taking other antidiabetic drugs2—the absolute risk 0.6%. And in April an analysis of data from the US Food and Drug Administration’s adverse event reporting system showed an increase in reports for pancreatitis and pancreatic cancer in people taking incretin mimetics compared with those taking other antidiabetic drugs.3

The FDA and EMA have both confirmed to the BMJ that their own analyses also show increased reporting or signals of pancreatic cancer with incretin mimetics. But they emphasise that this does not mean the relation is causal.

Both agencies announced in March that they will review data from a study just published showing pre-cancerous and dysplastic changes to the pancreas in organ donors exposed to incretin mimetics.4

The evidence is fiercely contested, with manufacturers stoutly defending the safety of their products. Merck, for example, told the BMJ that independent observational studies and a meta-analysis of clinical trials involving 33 881 patients found no association between DPP-4 inhibitors and pancreatic cancer. Bristol-Myers Squibb says that “post-marketing data does not confirm a causal relationship between saxagliptin or exenatide and pancreatitis and/or pancreatic cancer” (see for full questions and answers with manufacturers).

But a “Dear Doctor” letter from Bristol-Myers Squibb and AstraZeneca on the UK Medicine and Healthcare Products Regulatory Agency’s website says: “A review of reports of pancreatitis from post-marketing experience revealed that signs of pancreatitis occurred after the start of saxaglitpin treatment and resolved after discontinuation, which is suggestive of a causal relationship. Moreover, pancreatitis has been recognized as an adverse event for other DPP-4 inhibitors.”5 A spokeswoman for Boehringer Ingelheim told the BMJ: “Pancreatitis has been reported in clinical trials and spontaneous post marketing sources. Guidelines for the use of linagliptin in patients with suspected pancreatitis are included in the prescribing information of the treatment.”

The increasingly fractious debate among scientists and doctors was played out last month in the specialty journal Diabetes Care.

Experienced GLP-1 investigator, Professor Michael Nauck, head of the Diabeteszentrum in Bad Lauterberg, Germany, and a consultant to many of the manufacturers, argued that the published evidence against the drugs is weak. “The potential harms and risks typically refer to rare events and are discussed in a controversial manner,” he wrote.6 But a team of four academics from the US and UK (one an expert witness in litigation against one of the manufacturers) suggested that neither the safety nor the effectiveness of the class can be assumed. “The story is familiar. A new class of antidiabetic agents is rushed to market and widely promoted in the absence of any evidence of long-term beneficial outcomes. Evidence of harm accumulates, but is vigorously discounted,” they wrote in their response. 7

In the course of this investigation, the BMJ has reviewed thousands of pages of regulatory documents obtained under freedom of information and found unpublished data pointing to unwanted proliferative or inflammatory pancreatic effects.

The BMJ has also found that, despite published reports that indicated safety concerns, companies have not done critical safety studies; nor have regulators requested them. And access to raw data that would have helped resolve doubts about the safety of these drugs has been denied.

On their own, the individual pieces of unpublished evidence may seem inconclusive — increases in size and abnormal changes in animal pancreases, raised pancreatic enzyme concentrations in humans, reports of thyroid neoplasms, and pancreatitis in early clinical trials.

But when considered alongside other emerging and long standing evidence—such as concerns about the effect of GLP-1agonists on α cells first published in 19998; the presence of the GLP-1 receptor on cells other than the target pancreatic β cell; and increasing signals from regulatory databases2 9—a more coherent and worrying picture emerges, posing serious questions about the safety of this class of drug.

What’s going on in the pancreas?

In a world where the prevalence of type 2 diabetes is increasing rapidly, finding new targets for therapy is a high priority for drug companies. The discovery by scientists in the 1970s and the then publication in 1993 by Michael Nauck of the double action of GLP-1 (glucagon-like peptide-1) provided just such a target.

GLP-1 is a hormone-like peptide released by the intestine in response to a meal; its functions include regulating insulin and blood glucose and slowing gastric emptying. In his study, Nauck found that GLP-1 both increased the insulin made in the pancreas and, by inhibiting the secretion of glucagon, reduced the glucose released by the liver. Excessive glucose release by the liver underpins the high circulating glucose that defines type 2 diabetes. Following secretion, GLP-1 is quickly inactivated by an enzyme, dipeptidyl peptidase-4 (DPP-4). The GLP-1 drugs are either analogues that are not inactivated by DPP-4, taken by injection (exenatide, liraglutide) or oral drugs that inhibit DPP-4 (sitagliptin, saxagliptin, and linagliptin).

The saliva of the desert dwelling Gila monster was the source for the first GLP-1 analogue on the market, exenatide. A heavy slow moving lizard, it eats once or twice a year, and uses the secretion of its salivary hormone exendin-4—which displays similar properties to GLP-1—to induce proliferation of its pancreas and gut to assimilate a meal. Some say this should have provided a valuable clue to the unwanted effects of raised circulating levels of a hormone that usually lasts for only minutes before it is broken down.

But now that most of the other treatments for type 2 diabetes are off patent, these are valuable drugs. Merck’s market leading drug sitagliptin generated about $4.1bn (£2.6bn; €3bn) in sales in 2012 with liraglutide’s 2012 sales of $1.7bn coming in behind. The profit margins mean there is much at stake for the companies and the organisations and doctors who depend on their support.

However, serious doubts about the wisdom of basing treatments on GLP-1 agonists have existed since the beginning. And the companies and regulators have, on reflection, had in their hands ample warning signs—and chance to resolve some of the emerging controversies.

In 2005, the New England Journal of Medicine published a study that showed pancreatic changes in patients who had a type of gastric bypass surgery called Roux-en-Y. The authors noted hypertrophy and hyperplasia of the islet cells, also affecting the cells in the pancreatic ducts. They thought this might be due to raised levels of the hormone GLP-1, which were known to occur after this type of procedure.21 (A later study on this type of surgery also showed a “pronounced” increase in α cell mass22).

Senior executives from Amylin and Lilly wrote to the New England Journal to distance their drug from the paper and to stress the lack of evidence of a pathological effect on the islets in animal studies. “A study of nine months’ duration in healthy cynomolgus monkeys at doses of more than 400 times those used in humans showed minimal-to-mild islet hypercellularity with no increase in islet size (data on file, Amylin Pharmaceuticals),” they said.

The suppression of glucagon by incretin mimetics was highlighted by companies in their drug licensing applications and was noted by regulators. Billions of dollars of sales later, after concerns have been raised about the safety of glucagon suppression and its effect on glucagon producing α cells, the extent to which they do this is being contested.

Butler and colleagues’ finding of α cell hyperplasia in humans taking GLP1 based drugs4 was not the first. In 1999 GLP-1 researcher Joel Habener and a team at Harvard found that exendin-4 (exenatide) induced an increase in α cells in rats.8

But evidence of α cell hyperplasia has come from multiple models and sources—including the companies themselves. Whether this is applicable to GLP-1 based treatments is subject to fierce debate.

Only last October, Professor Dan Drucker, a long standing consultant to many of the companies, gave a keynote lecture at European Association for the Study of Diabetes conference. “The therapeutic window for reduction of glucagon action to manifest beneficial effects for glucose control while avoiding enhancement of hepatic lipid storage, dyslipidemia, hepatocyte injury, and α-cell proliferation in diabetic subjects is unclear,” the official conference journal reported.23

Others in industry have previously highlighted the important role of glucagon suppression in the control of diabetes. In 2005 at a session entitled “GLP-1s: the new darlings of diabetes treatment” Jens Holst, scientific director of the Novo Nordisk Foundation for Metabolic Research at Copenhagen University and a long standing consultant to the company, told the American Diabetes Association annual conference that GLP-1 agonists were a powerful inhibitor of glucagon secretion, adding that he thought this would be “a very important action to diabetes patients.”

A spokesperson for Novo Nordisk acknowledged an effect on α cells but only from full not partial glucagon suppression. She told the BMJ: “Complete removal or blocking of the glucagon receptor, or important signalling components, have caused α cell hyperplasia. This is separate from the relatively modest lowering of glucagon secretion induced by GLP-1.”

The BMJ asked Drucker about this. In response he sent a copy of an article he had written in Cell Metabolism, but this did not describe α cell effects.24 Yet the BMJhas found that the companies were aware of the unwanted effects of the full and partial suppression of glucagon before the incretin mimetics came onto the market.

At the turn of the century, Holst, working with scientists from Novo Nordisk, reported that glucagon suppression in mice resulted in massive enlargement of the pancreas and the proliferation of α cells (α cell hyperplasia).25 They concluded that α cells appear not just in the islets but in the pancreatic ductal epithelium—something that Butler and colleagues found. Importantly, this effect did not require complete blocking of glucagon receptors or the stopping of glucagon production. Even a partial reduction in the hormone signalling resulted in α cell hyperplasia, as shown by Eli Lilly in 2004.26 The Lilly team acknowledged that they hadn’t seen any neoplasia; the studies up until that point had been short—only four months long. They suggested that both glucagon and its receptor must be functional in order to maintain a feedback loop that restrains α cell growth “but the exact nature of this feedback loop is unclear.”26

Over the years, evidence of the effects of modifying glucagon signalling has mounted. In 2009 Run Yu, codirector of the carcinoid and neuroendocrine tumour programme at Cedars Sinai Hospital in Los Angeles, published a report in patients with a rare condition causing deficiencies in glucagon signalling.27 He found α cell hyperplasia and neuroendocrine tumours.

“In type 2 diabetes glucagon plays a role but there is a price to pay with reducing it,” he told the BMJ.

Yu said that he had shared his view with certain companies after the study came out. Because of agreements with the companies, he was unable to say which they were.

He then did a study in mice with decreased glucagon signalling that was far longer than any conducted by the companies. He found that neuroendocrine tumours invariably developed after formation of α cell hyperplasia and eventually led to death. Yu concluded that glucagon suppression was not a safe way to treat diabetes.28But whether this applies to GLP-1based therapies is still uncertain.

In the course of this investigation, the BMJ has looked at thousands of pages of regulatory documents from both the FDA and the EMA. There seems to be little discussion about the potential adverse effects of interfering with glucagon signalling on the α cell, even though the manufacturers spelt out —and the regulators noted—that glucagon suppression was one of the effects of the drugs. Michael Elashoff, a former FDA reviewer who has analysed the safety of the drugs, believes the regulators should have been more cautious in approving them.

“If some of the side effects can be anticipated in advance, then it seems incumbent upon the FDA to really force the companies to do real significant investigation of these potential side effects before the drug goes on the market and not leave it to experiment with actual patients taking the drug,” he said.

The FDA maintains that: “Long-term studies of incretin mimetics in rodents, dogs, and monkeys failed to demonstrate adverse pancreatic pathology or other toxicology reflective of a glucagon deficit that could be interpreted as a clear risk to human subjects.”

The BMJ asked the five companies who market incretin mimetics if they have ever studied the effects of glucagon suppression on the proliferation of α cells. Only Novo Nordisk responded to the question. It stressed that it had never seen α cell hyperplasia in any of its studies.29 30 31 “Alpha-cell hyperplasia is not mediated by the GLP-1 receptor,” a spokeswoman said. Behind the scenes, concerns also started to emerge about the potential inflammatory effects on the pancreas. Effects on pancreatic enzymes: Internal industry documents show that in 2005, one industry key opinion leader reported “extremely high” lipase levels in a patient taking exenatide. He was concerned that the company had missed signs of potential inflammation in its clinical trials.

Dennis Kim, then executive director at Amylin, wrote in an email that the doctor’s report was a “bit concerning” and confirmed that pancreatic amylase and lipase were not measured systematically in the company’s clinical trials.

The BMJ has found that companies have measured these enzymes for “safety issues,” but in many cases the data have not been reported in the published studies.

For example, in one Lilly funded trial comparing weekly exenatide with sitagliptin and two other diabetes treatments—insulin and pioglitazone—enzyme levels increased in a higher percentage of people taking incretin mimetics after 26 weeks of treatment.

Regulatory documents show the mean (SD) lipase concentration in the exenatide group increased from 42.0 (23.77) U/L on day 1 to 60.8 (38.39) U/L at week 26. Sitagliptin also increased lipase from 40.3 (21.3) U/L to 48.7 (30.7) U/L. The levels in the pioglitazone control dropped. However, when the trial was published in theLancet, these data did not make the final cut.32 The company did not say why when the BMJ put it to them. Neither did lead author, Richard Bergenstahl, answer theBMJ’s queries.

Earlier this year, the Lancet published another study funded by Eli Lilly and Amylin in which enzyme levels were measured but not reported.33 “Routinely measured concentrations of pancreatic lipase and total amylase varied in both groups and were not predictive of gastrointestinal symptoms,” the paper said.

The FDA says that the clinical value of routine amylase and lipase monitoring in asymptomatic patients is not clear. But pancreatologists, have told the BMJ that reporting enzyme levels is important because they may reflect a subclinical effect of the drug.

“Many large phase III trials report findings of significant biochemical abnormalities, even though the clinical significance may be uncertain at the time, and in this case where the drug is known to exert effects on the pancreas, I would find such information of value,” Thor Halfdanarson, a pancreatic surgeon, at the Mayo Clinic in Arizona said.

Indeed, writing in support of incretin mimetics in Diabetes Care last month, Michael Nauck said that the effect on pancreatic enzymes may be important.6 “Effects of GLP-1 receptor stimulation on pancreatic enzyme synthesis, potential leakage into the circulation rather than direct secretion into pancreatic digestive juice, and a potential induction if a chronic inflammatory response need to be studied,” he said.


Source: BMJ



Will we ever… eliminate animal experimentation?.


Arguably one of the most heated debates in science, efforts to reduce the number of animals used in studies face many barriers, says Alla Katsnelson.

One of the most, if not the most, contentious issues in science is the use of animals in research. Scientists experiment on animals for a host of different reasons, including basic research to explore how organisms function, investigating potential treatments for human disease, and safety and quality control testing of drugs, devices and other products. Its proponents point to the long list of medical advances made possible with the help of animal research. Opponents believe it is cruel and meaningless, as observations in animals often do not translate directly to humans.

In 1959, William Russell and Rex Burch proposed their “3Rs” guidelinesfor making the use of animals in scientific research more humane: restrict the use of animals; refine experiments to minimise distress; and replace tests with alternative techniques. Over the course of five decades their guidelines have become widely accepted worldwide, and while the reliability of published reports on the numbers used varies, they do at least provide a snapshot of historical trends. Around 29 million animals per year are currently used in experiments in the US and European Union countries. (Rats and mice make up around 80% of the total.) This is less than half the total in the mid-1970s – a significant drop, but one that has plateaued in the last decade.

“In the late 1980s, people thought animal research was singing its swan song,” says Larry Carbone, a senior veterinarian at the University of California in San Francisco. Fresh out of veterinary school in 1987, Carbone landed a job as an animal vet at Cornell University, in New York State. At that time the numbers of animals being used in experiments and testing was on the decline: the campus was building a new multi-storey biotechnology facility, with just three rooms containing animal breeding and living facilities.

But then came the development of tools that could selectively modify individual genes in mice. This proved to be such a powerful and popular technique that the decreasing trend in animal use ground to a halt.

Now, a raft of novel experimental techniques may help to push numbers down again. Improvements in imaging methods that offer a peek inside the bodies of animals allow scientists to get more and better data from each experiment than before. For example, researchers previously had to cull multiple mice at different stages of tumour development, but now they can non-invasively watch the disease unfold in a single living animal using a fluorescent dye. Similarly, as brain-imaging techniques become more advanced, some questions that are now addressed with experiments in monkeys might be better answered by peering into the human brain. “My prediction is that human volunteers will be able to replace monkeys more and more in the next 10-20 years,” says Carbone.

Meanwhile in vitro advances are also pointing towards reliable alternative methods. One such advance is the ability to re-program human skin cells into a primordial, stem cell-like state. These “induced pluripotent cells” could be converted into any specialised cell in the body, like liver or kidney cells, and these could be generated from people with a particular illness, giving researchers a potent and patient-specific model of that disease in a dish. Lab-on-a-chip technologies – and perhaps one day,lab-grown organs – could also provide increasingly sophisticated ways to identify disease mechanisms or test prospective medicines.

Finding alternatives

Trends also show that some sectors are doing more than others to reduce animal use. Some believe technological advances will one day make animal studies unnecessary, while others argue that “non-living” models will never be capable of reliably replicating all of the uses of laboratory mice and other creatures.

When many people think about animal testing, they imagine rows of rodent cages in a pharmaceutical company lab. But according to data from European Union countries, the pharmaceutical sector uses almost half the number of animals that academic labs do, and animal use in drug development dropped significantly between 2005 and 2008 – the most recent statistics available. There are two reasons for this, says Thomas Hartung, Director of the Center for Alternatives to Animal Testing at Johns Hopkins University, in Baltimore, Maryland. First, drugs are increasingly designed to target specific molecular mechanisms, and these are best identified in culture dishes rather than live animals. Second, conducting experiments in 1,536-well cell culture dishes is vastly less expensive than in animals, so companies are motivated to use alternatives whenever they are available.

In the US and the EU, a drug’s efficacy and safety must be tested in animals before it enters human testing, though a 2010 directive from the EU calls for alternatives to be used when possible. Jan Ottesen, vice president of lab animal science at Danish company Novo Nordisk, which makes insulin and other drugs for diabetes and haemophilia, says his company actively seeks out tests that can replace animal use without compromising patient safety. Novo Nordisk decided 15 years ago to replace animal tests with cell cultures to verify the quality of each batch of drugs before it goes to market. The company had to provide the authorities with data proving that other tests worked just as well. It took until 2011 for the company to complete the switch. 

However, for some types of experiments there are no equivalent non-animal options, says Ottesen. For example, in searching for new drugs that decrease joint pain due to arthritis, you need a model that mimics the human condition. The important thing, he stressed, is to set up the experiment so as to avoid unnecessary pain. For safety and toxicological testing of drugs, he adds, “I cannot see for the foreseeable future how we can completely avoid it. Having said that, all the replacements that can be implemented should be implemented.”

Under pressure

Safety testing of substances other than human and veterinary drugs, such as cosmetics, toiletries, household cleaning products and industrial chemicals might be a different story. Currently, says Hartung, such tests are outdated and inaccurate, with toxicity in rodents predicting problems in humans just 43% of the time. Meanwhile, tens of thousands of these substances have undergone no toxicity testing at all.

Addressing this gap with animal studies alone would be expensive and impractical. An overhaul of chemical safety regulations in the EU calledREACH and a toxicology modernisation initiative led by the US National Institutes of Health, are driving the search for alternatives.

Hartung believes that with enough investment and coordination, animal tests on products in this category can be replaced completely. He is leading the Human Toxome Project, an initiative that aims to map the ways substances disrupt hormones and endanger health, as well as to develop advanced, non-animal lab tests for toxicity testing. It’s slow going, Hartung concedes. “We don’t have human data to compare with, or really high-quality animal data,” he says, adding that this makes it tough to evaluate the quality of the tests.

Meanwhile, almost four in ten animals are used in basic, as opposed to applied, biological research – and this proportion is growing. Sarah Wolfensohn, a veterinary surgeon who heads Seventeen Eighty Nine, a consultancy advising researchers on animal welfare, based in Swindon, UK, says this is in part because a lot of this type of work is carried out in academia where the financial and performance pressures that motivate interest in non-animal-based techniques are weaker than in the commercial sector.

Other factors play a role too, she says. “For example, if a senior professor in academia has spent his entire career developing experimental techniques on monkeys’ brains and young researchers now tell him ‘actually we don’t need to do this, we can do it on a computer’, it undermines his approach.”

But just as important as reducing the numbers of animals used, adds Wolfensohn, is “to make sure they are being used in the best way and that their welfare is maximised, so as to get the best quality results, to make sure they are not wasted.”

Overall, pressure to limit the use of animals in research – either for financial, scientific or moral reasons – is rising. Meanwhile, the use of animals in many areas of life-science research is on the decline, experts note, even if genetic work in mice is still keeping numbers up. “I think this is temporary,” says Andrew Rowan, President and Chief Executive Officer of animal protection group Humane Society International. “I think it is going to start going down again as we improve our technologies.” How soon this might happen is too difficult to tell.

Source: BBC






Obesity treatment paradigms should target those at risk for diabetes.

Lifestyle modifications, weight-loss medications and bariatric surgery are the three major modalities that will have clinical implications on the prevention and treatment of obesity, according to data presented here.

“With effective options in all of these three treatment modalities, we can now evolve rational data-driven models of care that treat obesity as a medical illness,” W. TimothyGarvey, MD, professor and chair in the department of nutrition sciences at the University of Alabama at Birmingham, and senior scientist at the Nutrition Obesity Research Center, told Endocrine Today.

W. Timothy Garvey

Emerging therapies

During a presentation on emerging obesity therapies, Garvey reported recent data on phentermine-topiramate (Qsymia, Vivus) and lorcaserin (Belviq, Eisai), both of which gained approval in adults with an initial BMI of at least 30 or in those with a BMI of at least 27 and at least one weight-related condition, such as hypertension, type 2 diabetes or dyslipidemia.

“We’re in an exciting phase of drug development for obesity, with two drugs approved in the summer of 2012 that appear to be safe and effective for the treatment of obesity,” Garvey said.

“In addition, we have two other drugs that have finished or will soon finish phase 3 trials.”

One of these is bupropion/naltrexone (Contrave, Orexigen), an experimental agent now finished with phase 3 clinical trials. According to Garvey, a cardiovascular outcomes study is currently ongoing as requested by the FDA before approval. “The BP did not increase with the drug, but it didn’t go down to the extent that you’d predict with the weight loss achieved,” he said. “This will be the first cardiovascular outcomes study with a weight-loss drug where the data will be available in, perhaps, 2014.”

About an 8% weight loss was demonstrated and sustained during 1 year compared with 2% with placebo, Garvey said.

Furthermore, he referenced recent data from a 56-week, double blind, phase 3a clinical trial investigating higher-dose liraglutide (Victoza, Novo Nordisk) as a potential treatment for maintained weight loss in overweight or obese patients with type 2 diabetes. The manufacturer recently released the second phase 3a trial results from the clinical development program for liraglutide 3 mg as an obesity treatment.

“About 4 kg were lost on lifestyle intervention alone, and up to 9 kg were lost with high-dose liraglutide. There are 2-year data indicating that its efficacy for sustaining this weight loss is evident,” Garvey said.

Bariatric surgery

However, Garvey said medical and surgical interventions provide the best outcomes in obese patients with complications, and optimal benefit–risk occurs when weight loss is used as a tool to treat these complications of obesity.

As an adjunct to lifestyle modification, the aforementioned new medical therapies can result in a 10% loss of body weight, but if a patient begins with a BMI of 38, he will likely be obese when therapies are complete, Garvey said.

“However, that 10% loss of body weight is sufficient to improve insulin sensitivity, glucose homeostasis, lipid levels, BP, diabetes prevention, CVD risk factors and better control of both glucose and BP in patients with type 2 diabetes. We’re achieving an amount of weight loss here that’s in fact beneficial in terms of cardiometabolic disease,” he said.

Moving forward

Garvey concluded with the economic burden of diabetes and obesity on the United States health care system. He told Endocrine Today that for the clinical research community to address the diabetes and obesity epidemics, the progression from prediabetes to diabetes should first be considered.

“A rational and effective obesity treatment paradigm that targets resources to patients who are at highest risk will be cost-effective in preventing diabetes,” he said. “The numbers vary, but it costs much more per year to take care of a patient with diabetes than it does to take care of a patient without diabetes.”

Source: Endocrine today