Contrave Boosts Weight Loss in Diabetes Patients on Incretins

An exploratory evaluation means that the weight problems drug naltrexone/bupropion (Contrave, Orexigen Therapeutics) is secure and efficient for sufferers with sort 2 diabetes who’re obese or overweight being handled with an incretin for his or her diabetes and who want to drop extra pounds.

Notably, early responders who misplaced no less than 5% of their preliminary weight at 16 weeks and accomplished a yr of therapy with naltrexone/bupropion weighed eight.eight% lower than their beginning weight.

Researchers examined information from greater than 1000 sufferers with sort 2 diabetes who had participated in two older double-blind, placebo-controlled, section three research carried out earlier than sodium-glucose cotransporter-2 (SGLT2) inhibitors grew to become obtainable.

Sufferers have been taking a dipeptidyl peptidase-Four (DPP-Four) inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist, and had secure weight earlier than additionally being prescribed naltrexone/bupropion; they have been adopted for 1 yr.

Sean Wharton, MD, PharmD, from the Wharton Medical Clinic in Toronto, and McMaster College in Hamilton, Ontario, Canada, delivered the findings in an oral presentation through the digital American Diabetes Affiliation (ADA) 80th Scientific Classes.

There’s a message for clinicians, he informed Medscape Medical Information.

“If in case you have a affected person with diabetes and they’re on one of the best routine of a GLP-1 receptor agonist and their A1c comes down and their weight comes down,” however they nonetheless say they wish to lose just a little extra weight, “you possibly can add on Contrave and get additional weight reduction…in individuals who keep on it.”

The unwanted side effects, he mentioned, have been just like sufferers taking Contrave alone.

Equally, Contrave might be added to a DPP-Four inhibitor, which is weight impartial, for weight reduction in sufferers with obese or weight problems.

Scott Kahan, MD, MPH, director of the Nationwide Heart for Weight and Wellness, George Washington College, Washington, DC, who was not concerned within the research, mentioned: “This can be a precious preliminary consequence that deserves to be prolonged.”

“The outcomes are in keeping with prior analysis on naltrexone/bupropion for weight reduction, typically, in addition to for weight reduction therapy in sufferers with diabetes,” he informed Medscape Medical Information in an e-mail.

So it’s maybe not stunning, however “excellent news,” that naltrexone/bupropion was secure when used this fashion.

Nonetheless, “total, weight reduction with incretins is small,” he identified.

Taken collectively, this research helps that naltrexone/bupropion added to a GLP-1 agonist or different incretin “must be thought-about an affordable choice in sufferers with weight problems and sort 2 diabetes,” Kahan summarized.

Security and Efficacy of Naltrexone/Bupropion Added to an Incretin

A “whopping” 42% of US adults at the moment have weight problems and round 13% have diabetes, Wharton famous.

Along with their glucose-lowering impact, DPP-Four inhibitors and GLP-1 agonists have a impartial or favorable impact on weight, respectively.

And naltrexone/bupropion remedy acts to suppress urge for food and reduce cravings and is authorised for power weight administration.

However the security and efficacy of including naltrexone/bupropion for weight reduction in sufferers already on incretin remedy have been unknown.

To analyze this, the researchers carried out a retrospective evaluation of knowledge from the COR-DM research (Diabetes Care. 2013;36:4022-4029), carried out in 2007-2009, and the LIGHT research (JAMA. 2016;315:990-1004), carried out in 2012-2015.

As beforehand reported, the LIGHT research — which was to guage heart problems charges with naltrexone/bupropion — was controversially stopped in Could 2015 on account of leaked outcomes from 25% of deliberate enrollment. The section Four CONVENE trial, set to interchange the LIGHT research, was additionally ended, in April 2016, after Takeda bought the US rights for Contrave to Orexigen.

Most sufferers within the present research have been drawn from the sufferers with diabetes who took half within the LIGHT research.

Few sufferers got here from COR-DM, which excluded sufferers taking GLP-1 agonists.

The researchers recognized 4 affected person teams:

DPP-Four inhibitors and naltrexone/bupropion: 362 sufferers (345 from LIGHT)

DPP-Four inhibitors and placebo: 329 sufferers (317 from LIGHT)

GLP-1 agonist and naltrexone/bupropion: 339 sufferers (all from LIGHT)

GLP-1 agonist and placebo: 316 sufferers (all from LIGHT)

Sufferers have been a imply age of 60 years, had a imply physique mass index of 37-38 kg/m2, have been a imply weight of 105-109 kg (231-240 lb), and had a imply A1c of seven.Four%-7.5%.

The efficacy consequence was share change in weight from baseline to 1 yr.

At 1 yr, sufferers within the DPP-Four inhibitor and naltrexone/bupropion group had misplaced 5.9% of their preliminary weight, and people within the DPP-Four inhibitor and placebo group had misplaced 1.5% of their weight (P < .0001).

Equally, sufferers within the GLP-1 agonist and naltrexone/bupropion group misplaced 5.Four% of their preliminary weight and people within the GLP-1 agonist and placebo group had misplaced zero.2% of their weight (P < .0001).

Outcomes have been higher in “early responders” and “completers.”

There was no vital distinction in weight change between sufferers receiving a DPP-Four inhibitor or a GLP-1 agonist — however sufferers taking a GLP-1 agonist had already misplaced weight and had a secure weight at research entry.

The efficacy and security of naltrexone/bupropion within the present research have been just like that in research of contributors with out diabetes.

The most typical antagonistic occasions resulting in discontinuation of naltrexone/bupropion have been nausea (6.6% and 9.Four%) and vomiting and constipation (every lower than three%).  

COR-DM was funded by Orexigen Therapeutics and LIGHT was funded by Orexigen Therapeutics and Takeda Prescription drugs. The present research was funded by Bausch Well being Canada. Wharton has reported being on advisory panels for Bausch Well being and Novo Nordisk and receiving analysis assist from the Canadian Institutes of Well being Analysis and Novo Nordisk. Disclosures for the opposite authors are listed within the summary. Kahan has reported being a guide for Novo Nordisk and Vivus.

ADA 2020 Scientific Classes. June 13, 2020. Summary 141-OR.

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