The American Diabetes Association Commences its 82nd Scientific Sessions June 3-7 2022

Leading Diabetes Scientific Sessions Meeting Brings Together Researchers From Around the World With Hybrid Format 

NEW ORLEANS June 3, 2022– Today, the American Diabetes Association® (ADA) kicks off the 82nd Scientific Sessions in New Orleans, LA. The ADA’s Scientific Sessions is the world’s premier meeting in diabetes with a broader reach than ever with hybrid options for attendees. 

The meeting will take part live and virtually from around the globe today presenting the latest cutting-edge advances in diabetes research, prevention, and care. 

This year’s hybrid meeting will offer in-person opportunities for networking for more than 12 000 delegates, sharing the latest scientific findings with nearly 900 live presentations, more than 1,200 published posters, and over 80 exhibitors, as well as a virtual program for those unable to attend in person. 

Diabetes is the most common underlying chronic condition in the U.S. In fact, 133 million Americans currently live with diabetes or prediabetes and, in the last 20 years, the number of Americans with diagnosed diabetes has more than doubled. 

 

SURMOUNT-1 Study Finds Individuals with Obesity Lost up to 22.5% of their Body Weight when Taking Tirzepatide 

ADA June 4, 2022 – Today, findings from SURMOUNT-1, the first investigational phase 3 trial evaluating the safety and efficacy of t obesity, were announced, 

The trial 

2,539 participants who were obese or overweight with at least one weight-related condition, who do not have diabetes. The co-primary endpoints were percent change in body weight from baseline and greater percentage of participants achieving body weight reductions of at least 5% compared to placebo. The most commonly reported adverse events were gastrointestinal-related and generally mild to moderate in severity, usually occurring during the dose-escalation period. Nausea, diarrhea, and constipation were the most frequent adverse events. 

“Obesity should be treated like any other chronic disease—with effective and safe approaches that target underlying disease mechanisms, and these results underscore that effective therapeutic options for people with obesity. Notably, about 9 out of 10 individuals with obesity lost weight while taking tirzepatide.” 

Obesity impacts 650 million people worldwide and nearly half of Americans. Obesity is a chronic disease with limited treatment options that increases the risk of other weight-related conditions and negatively impacts overall health. 

This study aimed to evaluate tirzepatide, a once-weekly GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist, for the treatment of obesity. 

The findings indicate tirzepatide may be a potential therapeutic option for individuals living with obesity, with participants losing between 16% and 22.5% of their starting weight. The overall average weight reduction for the highest dose of tirzepatide (15 mg) was about 52 pounds or 20 kg. Substantial weight loss was also achieved on lower doses of tirzepatide: 35 pounds for the 5 mg dose and 49 pounds for the 10 mg dose. 

Tirzepatide had an overall safety and tolerability profile similar to other incretin-based therapies approved for the treatment of obesity.tirzepatide may be doing just that,” said Ania Jastreboff, MD, PhD, associate professor Yale University School of Medicine, director of Weight Management and Obesity Prevention at the Yale Stress Center and co-director of the Yale Center for Weight Management, New Haven, Connecticut. 

• “These results are an important step forward in potentially expanding irzepatide for the treatment of representing a new class of medicines being studied for the treatment of obesity. was presented at a symposium at the 82nd Scientific Sessions of the American Diabetes Association® (ADA) in New Orleans, LA, 

• Simultaneously published in The New England Journal of Medicine. 

https://www.nejm.org/doi/full/10.1056/NEJMoa2206038

Tirzepatide Once Weekly for the Treatment of Obesity

Abstract

BACKGROUND

Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known.

METHODS

In this phase 3 double-blind, randomized, controlled trial, we assigned 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Coprimary end points were the percentage change in weight from baseline and a weight reduction of 5% or more. The treatment-regimen estimand assessed effects regardless of treatment discontinuation in the intention-to-treat population.

RESULTS

At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was −15.0% (95% confidence interval [CI], −15.9 to −14.2) with 5-mg weekly doses of tirzepatide, −19.5% (95% CI, −20.4 to −18.5) with 10-mg doses, and −20.9% (95% CI, −21.8 to −19.9) with 15-mg doses and −3.1% (95% CI, −4.3 to −1.9) with placebo (P<0.001 for all comparisons with placebo). The percentage of participants who had weight reduction of 5% or more was 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35% (95% CI, 30 to 39) with placebo; 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% (95% CI, 1 to 5) in the placebo group (P<0.001 for all comparisons with placebo). Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively.

CONCLUSIONS

In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622. opens in new tab.)

EDITORIAL

https://www.nejm.org/doi/full/10.1056/NEJMe2206939?query=recirc_curatedRelated_article

Shifting Tides Offer New Hope For Obesity Clifford J. Rosen, M.D., and Julie R. Ingelfinger, M.D.

• Obesity is a chronic disease affecting millions of people — in 2020, the Centers for Disease Control and Prevention (CDC) reported that the overall prevalence of obesity in the United States during the period from 2017 through 2018 was 42.5%.The development of type 2 diabetes is a complication of obesity that leads to greater mortality primarily due to a higher incidence of cancer, cardiovascular disease, and kidney disease.  
• It is remarkable that the magnitude of weight loss with tirzepatide was similar to that with gastric bypass, which raises the potential for alternative medical approaches to the treatment of obesity.

_______

 

Tirzepatide Powers 'Unprecedented' Weight Loss in Obesity Trial

Treatment of people with obesity but no diabetes with the dual incretin agonist tirzepatide safely produced "unprecedented" levels of weight loss in the vast majority of patients in SURMOUNT-1, a placebo-controlled trial with more than 2500 people with obesity or overweight plus at least one weight-related complication.

Although the pivotal trial did not directly compare weekly subcutaneous injection of the twincretin tirzepatide (at 5 mg, 10 mg, or 15 mg) with either bariatric surgery or what has been the reigning champion of weight-loss agents, semaglutide injection 2.4 mg/week (Wegovy), the new findings are impressive, said Ania M. Jastreboff, MD, PhD, lead investigator of SURMOUNT-1, at the American Diabetes Association (ADA) 82nd Scientific Sessions.

First, the highest tested dosage of tirzepatide, 15 mg/week, over 72 weeks, produced a 5% or greater loss in baseline weight in 91%-96% of patients, an effect "not previously seen" in any prior phase 3 trial of a weight-loss agent, noted Jastreboff, an endocrinologist and director of weight management & obesity prevention at the Yale School of Medicine in New Haven, Connecticut.¨

Second, the average rate of weight loss among the 630 people who received tirzepatide 15 mg/week was 22.5% in the on-treatment analysis and 20.9% in the intention-to-treat analysis, again a magnitude of effect never before seen with any other medical intervention.

And in an exploratory analysis, 40% of people who received the highest-tested tirzepatide dose of 15 mg/week had at least a 25% loss in baseline weight in the on-treatment analysis, another example of unprecedented weight-loss achievement, said Jastreboff.

Looking at the data another way, the average baseline weight of those in the trial was 104 kg (230 lb) at the start, and the average weight loss was 35-52 lb by 72 weeks on treatment, Jastreboff told a press conference. 

She noted, however, that not everyone will respond to tirzepatide, "but if you do respond to this medicine, you will feel full earlier, you won't want to go back for seconds, and you may eat smaller amounts more often."  

Such weight loss agents will need to be taken chronically, similar to medications for hypertension and dyslipidemia, Jastreboff stressed. "If you stop the anti-obesity medication then the body fat mass setpoint will go back up, so this necessitates long-term treatment."

A New Era: Weight Loss "in the Range of Bariatric Surgery" 

Tirzepatide, developed by Lilly, has recently been approvedin the United States for the treatment of type 2 diabetes under the brand name Mounjaro.

SURMOUNT-1 was designed to examine the effect of the agent in overweight/obesity and the company will be filing for the additional indication of weight loss in the future. Topline results of SURMOUNT-1 generated much excitement when Lilly reported them back in April, including a story in The New York Times. 

Semaglutide, a Novo Nordisk drug, is approved in the United States for type 2 diabetes as Ozempic (at doses of 1 mg or 2 mg per week) and for weight loss as Wegovy (at the higher dose of 2.4 mg per week). When Wegovy was given the green light by the FDA a year ago, it too was hailed as a "gamechanger" for obesity.

The weight loss results seen in SURMOUNT-1 "put tirzepatide squarely in the range of weight loss achieved with bariatric surgery," concluded Louis J. Aronne, MD, a trial co-investigator, as well as professor and director of the Center for Weight Management and Metabolic Clinical Research at Weill-Cornell Medicine in New York City

The results are "amazing," and propel the weight-loss field into "a new era of obesity treatment," commented Lee M. Kaplan, MD, who was not involved in the study and served as designated discussant for the trial.

Despite the lack of direct comparison, the findings indicate that "tirzepatide causes more weight loss than semaglutide," and it provides "an opportunity to meet or exceed" the weight loss effects of bariatric surgery, added Kaplan, director of the Obesity, Metabolism and Nutrition Institute at the  Massachusetts General Hospital in Boston.

Simultaneously with Jastreboff's report at the meeting, the results were published online in The New England Journal of Medicine.

An accompanying editorial, agrees with Kaplan: "It is remarkable that the magnitude of weight loss with tirzepatide was similar to that with gastric bypass, which raises the potential for alternative medical approaches to the treatment of obesity."’

"The tides are shifting, and there are now more options for people with obesity to lose weight," write Clifford J. Rosen, MD, of Tufts University School of Medicine, Boston, and Julie R. Ingelfinger, MD.

Dual Incretin Agonism "Enhances Activity," Says Expert

Tirzepatide is the first agent on the US market from a novel class of dual-incretin agonists, with a molecular structure engineered to activate both the glucagon-like protein-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP), the two predominant incretins in the human gut. This combined activity has led to the twincretin nickname for tirzepatide.

Semaglutide is a single-incretin agonist, with its activity focused exclusively on the GLP-1 receptor.

Aronne tied the apparently superior efficacy of tirzepatide relative to semaglutide directly to the added incretin activity of tirzepatide. "The dual approach enhances efficacy," he proposed during his presentation at the meeting.

The impressive efficacy and reassuring safety profile reported from SURMOUNT-1 opens the door to a new approach to treating obesity, which in the past has often taken a back seat to treatments for dyslipidemia, hypertension, and diabetes.

"Now that we can treat obesity safely and effectively, it makes sense to treat obesity first," Aronne recommended.

Jastreboff agreed: "Perhaps we can prevent diabetes by treating obesity head-on," she remarked. 

Weight Loss Agents Gain US Traction

There have been concerns about patient access to these newer weight loss drugs in the United States, given that the retail cost of semaglutide for obesity exceeds $1000/month, but Aronne reported data that painted a more optimistic picture.

His numbers showed that during the first months that semaglutide was on the US market as a weight loss agent, the number of US prescriptions written for branded anti-obesity medications roughly doubled, a spike that seemed mostly driven by the introduction and growing use of semaglutide.

With tirzepatide, every prespecified cardiometabolic parameter assessed in the trial showed clinically meaningful improvements, reported Jastreboff, including an average 17% reduction in waist circumference in patients on either of the highest two dosages, a 34% average drop in total fat mass, an average 0.5 percentage point cut in baseline A1c at the highest two dosages, substantial cuts in fasting plasma glucose and fasting insulin levels,  an average 28% drop in triglyceride levels, and an average systolic blood pressure reduction of about 8 mm Hg that occurred within 24 weeks on treatment.

• "I think that insurers will sign up" for tirzepatide coverage based on benefits like this, Aronne predicted.

SURMOUNT-1 randomized 2539 patients with obesity or with overweight plus at least one weight-related complication at any of 119 sites in nine countries. They had a body-mass index (BMI) of 30 kg/m² or more, or 27 kg/m² or more and at least one weight-related complication, excluding diabetes. They were randomized, in a 1:1:1:1 ratio, to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period.

The study's two primary endpoints were the average percentage change in body weight from entry to 72 weeks, and the percentage of participants reaching at least a 5% reduction in their baseline body weight by 72 weeks.

The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively

The trial ran from December 2019 to April 2022, so during the peak of the COVID-19 pandemic, which Jastreboff described as an "amazing feat."

Jamy Ard, MD, who chaired the SURMOUNT-1 session quipped, after hearing the results, "Wow; that's exciting. If you're not excited by the results, you'd better check your pulse."

Ard is a professor at Wake Forest University School of Medicine and co-director of the Wake Forest Baptist Health Weight Management Center.

SURMOUNT-1 was sponsored by Eli Lilly, the company that markets tirzepatide (Mounjaro). 

 

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