Type 2 Diabetes and weight loss medication

Type 2 diabetes and obesity affect millions across the globe, creating a significant demand for effective treatments. GLP-1 Receptor agonists such as Ozempic (Semaglutide) & Mounjaro (Tirzepatide) have become the blockbuster drugs of the past decade. Although these drugs are highly effective in treating type 2 diabetes & facilitating weight loss, often lead to muscle mass reduction—a concerning side effect.

They also come with a number of other side effects, not to mention the rebound weight gain when these drugs are stopped. Also, 10% of the population are trypanophobes (fear of needles) which makes using these drugs long term a problem.

Recent research from Swedish scientists introduces a promising new oral medication designed to treat type 2 diabetes and promote weight loss without the detrimental side effect of muscle loss. This innovative drug works by stimulating skeletal muscle metabolism, which aids in preserving muscle mass during weight reduction. The preliminary phase 1 clinical trial, involving both healthy participants and those diagnosed with type 2 diabetes, indicated good tolerance, setting the stage for a more extensive phase 2 trial focused on evaluating its effects on muscle mass, glucose levels, and insulin sensitivity.

Unlike GLP-1 drugs, which primarily function by suppressing hunger and slowing gastric emptying, the new medication promotes metabolism specifically in skeletal muscle. Muscle tissue plays a critical role in energy expenditure and glucose regulation; thus, preserving muscle is vital for maintaining metabolic health during weight loss.

The new drug is developed based on a beta-2 molecule, typically associated with cardiovascular risks. However, the researchers are optimistic that their formulation minimizes these risks, leading to minimal or no adverse cardiac effects.

Retaining muscle mass during weight loss is crucial not just for strength, but also for sustaining metabolic rate and managing blood sugar levels. The fight against obesity and diabetes intensifies as effective strategies emerge that prioritize muscle preservation alongside fat loss.

It should not be about weight loss, but rather, fat loss.

Another drug, Orforglipron is a novel small-molecule, nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist being evaluated for the treatment of type 2 diabetes and weight management. The study aimed to gather more data on its efficacy and safety. 

A phase 3, double-blind, placebo-controlled trial was conducted with participants who had early type 2 diabetes being treated solely with diet and exercise. A total of 559 participants were randomly assigned to receive one of three doses of orforglipron (3 mg, 12 mg, or 36 mg) or a placebo daily for 40 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) levels, while a secondary endpoint focused on the percent change in body weight.

The 40 week trial demonstrated that varying doses of orforglipron achieved some degree of weight loss & control of diabetes without the need for injections.

A new monthly weight loss injection, MariTide,  demonstrated significant effectiveness in a phase 2 clinical trial, with participants losing up to 20% of their body weight over the course of a year. MariTide operates by targeting a hormone that slows gastric emptying, offering an alternative to existing weekly injected GLP-1 drugs like Ozempic and Wegovy.

The trial included nearly 600 adults, both with type 2 diabetes and obesity, and individuals with obesity alone.

Results indicated that participants with obesity lost an average of 20% of body weight on MariTide compared to just 2.6% for the placebo group. For participants with diabetes, the average weight loss was 17%, compared to 1.4% in the placebo group.

MariTide also lowered blood sugar levels, with a reduction in the A1C level by as much as 2.2 percentage points for those with diabetes, surpassing the results of some existing treatments.

In addition to weight loss, participants experienced improvements in cardiovascular health indicators, including blood pressure, cholesterol, and inflammation.

Amgen plans to initiate a phase 3 trial for MariTide, although regulatory approval is likely still years away. The move to a monthly dosing regimen is expected to provide convenience for patients, making it an attractive option for those managing obesity and diabetes. Side effects were comparable to other GLP-1 medications, primarily involving gastrointestinal issues.

Regardless of all these new innovations in the weight loss space, there is no doubt the best approach is through significant dietary change (80%) & exercise (20%). It is a tragedy that most modern day humans do not have the discipline & perseverance to be able to achieve ideal body weight, better control of type 2 diabetes & no doubt, overall better health.