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People living with obesity are at a higher risk of developing type 2 diabetes and cardiovascular disease. While losing weight significantly reduces these risks, often diet and exercise are not enough. In recent years, new research has addressed the dual health crisis of obesity and diabetes, with studies promising new treatment options for type 2 diabetes and weight management for obesity.

Findings from three studies presented at the recent 84th American Diabetes Association (ADA) Scientific Sessions, held in Orlando, Florida, from June 21 to 24, showcased the latest developments in treatments for obesity, including GLP-1 (Glucagon-like peptide-1) receptor agonists.

HRS9531 shows promise as a treatment for obesity

Results from a phase 2 trial evaluating the efficacy and safety of HRS9531 — a dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonist — suggest that the medicine could be a promising treatment option for people with overweight or obesity and type 2 diabetes.

The double-blind, randomised, placebo-controlled Phase 2 trial evaluated the efficacy and safety of HRS9531 in obese adults without diabetes. In five randomised groups, 249 Chinese adults with a BMI of 28-40 kg/m²v received once-weekly subcutaneous injections of HRS9531 (1.0 mg, 3.0 mg, 4.5 mg, and 6.0 mg) or a placebo for six months. The objective was to measure weight loss percentages at the trial’s end.

Outcomes showed that HRS9531 effectively reduced body weight, blood pressure, blood glucose, and triglycerides, with a favourable safety profile consistent with other GLP-1 agonists. Side effects were mild or moderate, occurring primarily during dose escalation. The most common were nausea, diarrhoea, decreased appetite and vomiting.

Furthermore, participants receiving HRS9531 experienced more significant weight loss than those receiving a placebo. At the end of the 24-week study, participants in the 1.0 mg, 3.0 mg, 4.5 mg, and 6.0 mg HRS9531 groups achieved weight loss of 5.4%, 13.4%, 14.0%, and 16.8%, respectively, compared with 0.1% in the placebo group.

Moreover, in each group, participants who lost 5% or more weight represented 52.0%, 88.2%, 92.0%, 91.8%, and 10.2%, respectively.

A phase 3 study with HRS9531 in Chinese overweight or obese individuals is already underway, with multi-regional studies in the pipeline.

Pemvidutide reveals weight loss up to 15.6%

The phase 2 MOMENTUM trial of pemvidutide, a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist, revealed promising results. After treatment, participants significantly reduced their body weight and serum lipids while conserving lean body mass.

Pemvidutide is in development for obesity and metabolic disorders associated steatohepatitis (MASH), a liver disease, and to help people with overweight and obesity lose weight.

This double-blind, randomised, placebo-controlled Phase 2 trial enrolled 391 participants with overweight or obesity but without diabetes. Each participant received either pemvidutide in three doses (1.2, 1.8, 2.4 mg) or a placebo weekly for 48 weeks.

At the end of the trial, participants receiving the highest pemvidutide dose (2.4 mg) had lost an average of 15.6% of their total body weight, and the treatment appeared to be safe and well-tolerated.

The study identified several possible advantages for weight loss, including a simple dosing regimen and significant decreases in lipids, such as cholesterol and triglycerides, which could reduce the risk of cardiovascular disease.

Additional results indicated participants conserved a favourable portion of lean mass, as shown in a body composition analysis — an assessment of the fat proportion to fat-free mass. Only 21.9% of weight loss was lean mass and 78.1% fat. Preserving lean mass, which primarily includes muscle, is believed to be critical for maintaining physical function and decreasing the risk of bone fractures.

A more extensive Phase 3 study is in the pipeline with registrational trials intended to demonstrate the safety and clinical benefit of pemvidutide for weight management. Because obesity can lead to the accumulation of excess liver fat and MASH, the authors are also studying pemvidutide in people with this condition.

Retatrutide improves insulin’s ability to lower blood glucose

A study within phase 2 clinical trials of retatrutide evaluated biomarkers to understand its effect on insulin-making pancreatic beta cells and biomarkers for insulin sensitivity. Biomarker analyses help understand diseases and identify specific therapeutic targets.

The study showed that retatrutide increased the secretion of insulin-producing beta cells (HOMA2-B) and insulin sensitivity. The results also demonstrated how retatrutide decreased stress markers in insulin-producing cells. This was assessed by measuring immature insulin (proinsulin) and reduction in a marker of insulin resistance (HOMA2-IR).

Several phase 3 clinical trials are underway to study retatrutide in people with type 2 diabetes or obesity without type 2 diabetes, including the TRIUMPH and TRANSCEND phase 3 trials.

Obesity is a progressive condition with many medical, physical and psychosocial issues, including a greater risk for type 2 diabetes. Over 85% of people with type 2 diabetes have overweight or obesity. The findings from these studies can enable a future with more effective obesity and type 2 diabetes management to improve the lives of people affected and reduce their public health impact.

Obesity and type 2 diabetes: a joint approach to halt the rise

Learn more about the connections between obesity and type 2 diabetes and the importance of joint action to tackle the rising prevalence of both conditions in this IDF D-Talk podcast.

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