Beyond GLP-1: Hope and Facts About New Weight-Loss Medicines

Written by Dr. Sarat Anandh, MD DVL

Medical Council registered dermatologist · 5 August 2026

Weight-loss medicines are moving from single-hormone to dual- and triple-hormone action. Here is what the evidence really says—and why medical supervision still matters.

Why these medicines are changing weight-loss care

For many people, weight is not simply about willpower. Appetite, fullness, blood sugar, sleep, medicines, hormones and genetics can all influence how the body manages weight. This is why modern obesity care may include medication alongside food choices, movement, sleep and behavioural support.
GLP-1 medicines have changed this field by helping some people feel full earlier and remain satisfied for longer. Newer medicines act on two or even three hormone pathways. They may produce greater average weight reduction in clinical trials, but they also require thoughtful prescribing, gradual dose increases and regular follow-up.

GLP-1, dual and triple agonists explained simply

GLP-1 receptor agonists, such as semaglutide, copy some actions of a natural gut hormone. They influence appetite and fullness, slow the movement of food through the stomach and support glucose-dependent insulin release.

In the STEP 1 trial, adults with overweight or obesity without diabetes received weekly semaglutide 2.4 mg or placebo, together with lifestyle support. At 68 weeks, the average weight change was approximately 14.9% with semaglutide and 2.4% with placebo. These were group averages, not a promise of what every patient will experience.

Tirzepatide activates both GIP and GLP-1 receptors. These two signals work together on appetite and metabolic control. In the 2025 SURMOUNT-5 head-to-head trial involving adults with obesity without diabetes, average weight reduction at 72 weeks was 20.2% with tirzepatide and 13.7% with semaglutide, using the maximum tolerated doses. Digestive side effects were the most common in both groups and occurred mainly while doses were being increased.

These findings do not mean that the medicine producing the larger trial average is automatically right for every person. Your health conditions, current medicines, tolerance, goals and ability to continue treatment all matter.

What is the GLP-1 + GIP + glucagon medicine?

Retatrutide is a once-weekly investigational injection that activates three receptors: GLP-1, GIP and glucagon. The added glucagon action is being studied for its possible effect on energy use and metabolism, alongside the appetite-related effects of GLP-1 and GIP.

In a phase 2 obesity trial, the highest-dose retatrutide group had an average weight reduction of 24.2% at 48 weeks. However, this was an earlier-stage study with specific eligibility rules and close research monitoring. It should not be compared casually with results from separate semaglutide or tirzepatide trials because the participants, doses and study lengths were different.

Phase 3 results have since been announced, but retatrutide remains investigational and has not been approved by any regulatory agency as of July 2026. Some detailed results still await peer-reviewed publication and regulatory assessment. Products sold online or through unofficial channels as “retatrutide” may have uncertain ingredients, strength, purity or sterility and should not be used.

Safety matters as much as weight change

Nausea, vomiting, diarrhoea, constipation and abdominal discomfort are among the commonly reported side effects of these medicine classes. Starting at a low dose and increasing slowly may help, but some people still cannot tolerate treatment. Severe or continuing symptoms require medical review.

Before prescribing, a doctor should review your medical history, other medicines and weight-related conditions. Tell your doctor if you are pregnant, breastfeeding or planning pregnancy, or if you have had gallbladder problems, pancreatitis or significant digestive symptoms.

Treatment should also protect nutrition and daily function. The plan may include adequate protein, strength-based activity, hydration, fibre and monitoring of symptoms and progress. Simply eating as little as possible is neither the goal nor a safe strategy.

Obesity is a chronic condition, and weight can return after medication is stopped. Current clinical guidance therefore treats medication as part of a longer-term, individualised plan rather than a brief crash programme. Any decision to continue, change or gradually stop treatment should be made with the prescribing doctor.

At The Derm Edit in Anna Nagar and Mogappair, Chennai, Dr. Sarat Anandh, MD DVL, is a double gold-medalist and Medical Council registered dermatologist. Your consultation can include a review of medical suitability, realistic goals, nutrition, movement and follow-up needs. Message us on WhatsApp for details.