By Dr. Asnat Raziel, specialist in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal
New weight loss injections: what has really changed
New weight loss injections are changing the way we treat obesity. A decade ago, losing 5% to 10% of body weight counted as a good success. Today, in large trials, some drugs reach an average of 20% and even more. However, not every drug that makes the headlines is already available. So it is important to separate what is approved today from what is still under study.
In this article, I review the existing drugs, the ones on the way, and what to ask before you start. I will also explain why the injection is only one part of treatment.
How do the new drugs work?
Most drugs in this field mimic hormones that the gut releases after a meal. The main hormone is GLP-1, which slows stomach emptying and signals fullness to the brain. As a result, appetite drops and the “noise” around food fades.
Beyond GLP-1, the next generation activates additional pathways. For example, GIP is a second gut hormone that improves blood sugar control. Amylin is a hormone the pancreas releases together with insulin, and it adds to the feeling of fullness. Glucagon, in contrast, increases energy burning and fat breakdown in the liver. The more pathways a drug combines, the greater the weight loss in trials. At the same time, side effects also need monitoring.
New weight loss injections that are already approved
Tirzepatide (Mounjaro)
Tirzepatide, sold as Mounjaro, acts on two receptors: GLP-1 and GIP. That is why doctors call it a “dual agonist”. For example, the SURMOUNT-1 trial studied 2,539 adults with obesity and without diabetes. After 72 weeks, average weight loss at the 15 mg dose reached 20.9%, compared with 3.1% in the placebo group. More background on the drug is available in the encyclopedia entry on tirzepatide (Mounjaro).
High-dose semaglutide (Wegovy)
Semaglutide, sold as Wegovy, has until now been given at a weekly dose of 2.4 mg. Recently, the US Food and Drug Administration (FDA) also approved a 7.2 mg dose. In the STEP UP trial, the comparison between doses showed an average loss of 18.7% at the high dose, compared with 15.6% at the standard dose. On the other hand, a tingling or sensitive feeling in the skin (dysesthesia) occurred in 22.9% of patients on the high dose. I covered this in detail in my article on Wegovy at the 7.2 mg dose.
It is also worth knowing that the US institute NIDDK publishes an updated list of FDA-approved drugs for treating overweight. The list also includes older drugs, which still suit some patients.
New weight loss injections still on the way
CagriSema: a combination with amylin
CagriSema combines semaglutide with cagrilintide, a drug that mimics amylin. The REDEFINE 1 trial enrolled 3,417 adults without diabetes. After 68 weeks, average weight loss was 20.4%, compared with 3.0% on placebo. However, digestive side effects occurred in 79.6% of patients, mostly transient and mild to moderate. Novo Nordisk submitted the drug for FDA approval in December 2025. As of mid-October, no decision had been made.
Retatrutide: three pathways in one injection
Lilly’s retatrutide acts on GLP-1, GIP and glucagon. The TRIUMPH-1 trial enrolled 2,339 adults with obesity. According to the company’s announcement, average weight loss at the 12 mg dose reached 28.3% after 80 weeks. Even so, 42.4% reported nausea at this dose, and 11.3% stopped treatment because of side effects.
Later, two further trials, TRIUMPH-2 and TRIUMPH-3, showed weight loss of up to 20.8% in people with diabetes. They also showed up to 22.6% in patients with heart disease. Lilly plans to submit the drug to the FDA in the first quarter of 2027. Moreover, the full data have not yet appeared in a journal. I summarized the findings in my guide to retatrutide.
An injection once a month
Another research direction is a longer gap between injections. For example, Amgen’s MariTide is now in phase 3 trials as a monthly injection. Meanwhile, pill options are also available today, such as Foundayo (orforglipron).
Who are new weight loss injections suitable for?
The accepted indication is a BMI of 30 or more, or a BMI of 27 or more with a related condition. Such conditions include, for example, high blood pressure, fatty liver, prediabetes or sleep apnea. In addition, doctors review medical history, other medications and pregnancy plans.
In Israel, coverage varies by drug, age and health fund. At Maccabi, for example, Wegovy is included in the health basket for ages 12 to 17 under set conditions. Adults receive a subsidy through supplementary insurance. Therefore, it is worth checking your personal eligibility in advance.
Side effects of new weight loss injections
The common side effects are similar across all drugs in this group: nausea, diarrhea, constipation and vomiting. Most of them appear at the start of treatment or after a dose increase. For this reason, doctors raise the dose gradually, according to each person’s response. Small meals, enough fluids and less fatty food help most patients.
Furthermore, part of the weight lost is muscle mass. Eating enough protein and doing strength training are part of the treatment itself. I set out the principles in my article on how to prevent muscle loss while losing weight. For a broad review, see my guide to the side effects of weight loss drugs.
New weight loss injections are part of a plan
Obesity is a chronic disease. When patients stop the drug, most of them regain weight. Therefore, treatment requires a long-term plan rather than a short “course”. At our clinic, we combine a doctor, a dietitian and tailored physical activity. Ultimately, the goal is better health, not just a number on the scale.
The bottom line
Today, new weight loss injections allow weight loss that in the past almost only surgery achieved. Mounjaro and high-dose Wegovy are already approved in the US, while CagriSema and retatrutide are getting closer to approval. Still, the choice of drug should be personal, with medical follow-up and support for nutrition and activity. If you are considering treatment, a talk with a doctor who specializes in obesity is a good first step.
This article provides general information and is not personal medical advice. For any question about your treatment, please consult your doctor.
Questions and answers
What is the difference between Mounjaro and Wegovy?
Wegovy acts on one receptor, GLP-1. Mounjaro acts on two, GLP-1 and GIP. In a direct head-to-head trial, average weight loss with Mounjaro was greater than with Wegovy at 2.4 mg.
When will retatrutide be available?
Lilly plans to submit it to the FDA in the first quarter of 2027. Doctors will be able to prescribe it only after approval in the US and in Israel.
Can I stop the injections once I reach my target weight?
You can, but most patients regain weight. That is why you plan ahead with your doctor whether to lower the dose, continue or switch to another treatment.
Is there an alternative to an injection?
Yes. Today there are also pills, such as the Wegovy pill and Foundayo. Their effectiveness is not the same, and you make the choice together with your doctor.
References
Tirzepatide Once Weekly for the Treatment of Obesity
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity
Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial
Lilly’s triple agonist, retatrutide, successful in two additional Phase 3 obesity trials
Prescription Medications to Treat Overweight & Obesity
Injections for the treatment of obesity and diabetes – Maccabi Healthcare Services (in Hebrew)
