The new wave of weight-loss injections: what you should know

The last two years have transformed medical treatment for obesity. Weekly “metabolic” injections are helping many people lose 15–25% of body weight—approaching results once seen only with bariatric surgery—and some now carry proven heart-protection benefits. Here’s a clear, up-to-date guide to what’s approved, what’s coming next, who’s eligible (UK & beyond), and the safety points to discuss with your clinician.

1) What are these medicines?

Most of today’s shots mimic gut hormones that regulate appetite and metabolism.

• GLP-1 receptor agonists (e.g., semaglutide at weight-loss dose branded Wegovy).
  In March 2024, the FDA added an indication to reduce major cardiovascular events (heart attack, stroke, CV death) in adults with overweight/obesity who already have cardiovascular disease—first in class to show this. U.S. Food and Drug Administration+2PR Newswire+2
• Dual GIP/GLP-1 agonists (e.g., tirzepatide, branded Zepbound for obesity/Mounjaro for diabetes) deliver even larger average weight loss than semaglutide in head-to-head trials in people with obesity but without diabetes. New England Journal of Medicine

How much weight do people actually lose?

• In pivotal trials, tirzepatide cut body weight by ~20% at 72 weeks; semaglutide 2.4 mg averages ~15%–16%. (Exact results vary by study, dose and population.) New England Journal of Medicine

Do these drugs improve heart risk?

• Beyond the 2024 FDA label for semaglutide, a large real-world analysis presented in 2025 suggested semaglutide users had lower short-term rates of major cardiac events than tirzepatide users; note this was observational (not randomized). Reuters

2) Who can get them? (UK snapshot)

• England/NICE recommends Wegovy (semaglutide) for adults meeting BMI and service criteria; treatment is reassessed if <5% weight loss at 6 months. NICE+1
• In Dec 2024, NICE recommended tirzepatide for managing overweight and obesity in adults—generally BMI ≥35 kg/m² plus at least one weight-related comorbidity (with lower BMI thresholds for some ethnic groups). Guidance reviewed Sept 2025. NICE+2NICE+2

(Access, criteria, and pricing differ by country; check your local guidance.)

3) Safety, side effects, and surgery

Common effects: nausea, vomiting, diarrhoea/constipation—usually dose-related and often ease with slow titration. Gallbladder events (gallstones, cholecystitis) occur more often with semaglutide than placebo and can be linked to rapid weight loss. Pancreatitis has been reported with GLP-1 drugs—seek urgent care for severe, persistent abdominal pain. These warnings appear in official U.S. labels for semaglutide (Wegovy/Ozempic) and oral semaglutide (Rybelsus). FDA Access Data+3FDA Access Data+3FDA Access Data+3

Lean mass: part of the lost weight is lean (not just fat). Reviews and imaging studies suggest ~20–50% of lost weight can be lean mass without counter-measures, so clinicians emphasize adequate protein + resistance exercise to preserve muscle and function. ScienceDirect+2AHA Journals+2

Before procedures/anaesthesia: GLP-1s can delay stomach emptying, raising aspiration concerns. Early 2023–2024 guidance suggested withholding before elective procedures; later multi-society guidance (Oct 2024) concluded most patients can continue, with individualized risk assessment (e.g., consider liquid diet or adjustments for those with significant GI symptoms). Discuss timing with your surgical team. American Society of Anesthesiologists+3American Society of Anesthesiologists+3Wiley Online Library+3

Counterfeits & gray-market sales: Demand has led to fake or unregulated products—including recent UK reports and a WHO alert on falsified semaglutide batches. Only use regulated supply chains. Reuters+1

4) What happens if you stop?

Obesity is chronic and biologically defended. In a 2023–2024 tirzepatide maintenance study, those who stopped regained substantial weight; continuing therapy maintained or improved prior loss. Expect a long-term plan (medicine + lifestyle + monitoring). JAMA Network

5) The pipeline: what’s next?

A faster, more potent wave is coming—still investigational for most patients today.

• Retatrutide (triple agonist: GIP/GLP-1/glucagon)
  Phase 2 showed up to ~24% mean loss at 48 weeks; not approved anywhere as of now. Beware illicit sales advertised online. New England Journal of Medicine+1
• CagriSema (cagrilintide + semaglutide, once weekly)
  Phase 3 REDEFINE-1/2 reported ~20–23% loss without diabetes and ~15–16% with diabetes over 68 weeks; GI side-effects similar to GLP-1 class. (Still investigational for weight management in most regions.) New England Journal of Medicine+2New England Journal of Medicine+2
• Amycretin (unimolecular GLP-1 + amylin)
  Phase 1/2 program reported ~24% loss at 36 weeks in early studies; larger trials are underway. ScienceDirect+1

These candidates hint at deeper average losses and possibly broader metabolic benefits, but availability will depend on Phase 3 outcomes and regulators. Clinical Trials Arena

6) Practical tips for patients

Ask at the start

• Am I eligible under local guidance (e.g., NICE), and what’s realistic for me? NICE
• How will we protect muscle and bone? (programmed protein intake + resistance training). advances.massgeneral.org
• What’s our plan around surgery/endoscopy? (coordinate with anaesthetics team). American Society of Anesthesiologists
• How long will I stay on treatment, and what’s our maintenance plan? (expect long-term management). JAMA Network

Use safe channels only
Given counterfeit risks flagged by WHO and UK media investigations, avoid online sellers and “research” vials; confirm your product and pen are authentic pharmacy supply. Reuters+1

Track more than the scale
Log waist, strength, stamina, and labs (A1c, lipids, BP). Some benefits (e.g., cardiovascular risk reduction with semaglutide in CVD) go beyond kilograms. U.S. Food and Drug Administration

7) Key takeaways

• Today’s standard: once-weekly semaglutide and tirzepatide deliver ~15–20% average weight loss in trials; semaglutide also has an FDA-approved CV-risk indication for people with established CVD. New England Journal of Medicine+1
• Tomorrow’s horizon: retatrutide, CagriSema, amycretin and others may push average losses into the 20–25% range, pending Phase 3 and approvals. None are over-the-counter; avoid gray-market versions. New England Journal of Medicine+2New England Journal of Medicine+2
• Safety: GI side-effects are common; watch for gallbladder issues and rare pancreatitis; plan for muscle preservation and discuss peri-operative timing. American Society of Anesthesiologists+3FDA Access Data+3FDA Access Data+3
• Sustainability: Expect long-term treatment and a lifestyle program; stopping often leads to regain. JAMA Network