Tirzepatide vs semaglutide: the head-to-head trials, for Belize

Belize's Ministry of Health and Wellness estimates that one in four Belizeans lives with hypertension and one in six with diabetes¹. In October 2025 Cabinet asked the Ministries of Health and Finance to explore ways to reduce the cost of certain classes of drugs used for noncommunicable diseases¹¹. For physicians weighing incretin-based drugs, the question has changed. It used to be whether these peptides work against placebo. Now two randomized trials have compared tirzepatide, a dual GIP and GLP-1 receptor agonist, directly with semaglutide, a GLP-1 receptor agonist. This is what they show.

SURMOUNT-5: tirzepatide vs semaglutide in obesity

SURMOUNT-5 randomized 751 adults with obesity but without type 2 diabetes to the maximum tolerated dose of tirzepatide or of semaglutide, once weekly for 72 weeks². Mean weight change was −20.2 % with tirzepatide and −13.7 % with semaglutide (P<0.001); waist circumference fell 18.4 cm and 13.0 cm². More tirzepatide participants reached weight losses of at least 10 %, 15 %, 20 % and 25 %². The most common adverse events in both groups were gastrointestinal, mostly mild to moderate and concentrated in dose escalation². A subgroup analysis of 383 participants meeting Japanese obesity-disease criteria found the same pattern, −20.1 % versus −12.9 %¹². For context, the placebo-controlled trials that preceded it reported −14.9 % with semaglutide versus −2.4 % with placebo at 68 weeks (STEP 1)⁹ and −15.0 % to −20.9 % with tirzepatide versus −3.1 % at 72 weeks (SURMOUNT-1)¹⁰.

SURPASS-2: the comparison in type 2 diabetes

SURPASS-2 randomized 1,879 adults with type 2 diabetes, mean HbA1c 8.28 %, to one of three tirzepatide arms or to semaglutide for 40 weeks³. HbA1c fell 2.01 to 2.30 percentage points with tirzepatide and 1.86 with semaglutide; every tirzepatide arm was noninferior and superior, with differences of −0.15 to −0.45 points³. Weight reductions were greater with tirzepatide by 1.9 to 5.5 kg³. Gastrointestinal events were similar (nausea 17–22 % versus 18 %), but serious adverse events were reported in 5–7 % of tirzepatide patients and 3 % of semaglutide patients³.

Hard outcomes: where semaglutide has more data

Weight and HbA1c are surrogate endpoints. On hard outcomes the evidence is uneven. In SELECT, 17,604 adults with cardiovascular disease and overweight or obesity but no diabetes had a primary cardiovascular event in 6.5 % of the semaglutide group versus 8.0 % with placebo (hazard ratio 0.80)⁴. In FLOW, semaglutide reduced major kidney outcomes in type 2 diabetes with chronic kidney disease (hazard ratio 0.76) and lowered death from any cause by 20 %⁵. Tirzepatide's cardiovascular trial, SURPASS-CVOT, used an active comparator: among 13,299 patients with type 2 diabetes and atherosclerotic disease, events occurred in 12.2 % with tirzepatide and 13.1 % with dulaglutide (hazard ratio 0.92), meeting noninferiority but not superiority⁶. Cost models are favourable to tirzepatide: a US analysis of SURMOUNT-5 data, with Eli Lilly employees among its authors, estimated lower total costs and more quality-adjusted life years⁷. That model used US prices and has not been tested for Belize⁷.

What Belize's rules and PAHO's guidance mean

Any GLP-1 or dual agonist sold in Belize must hold registration and a product licence under the Food and Drugs (Registration, Licensing and Inspection) Regulations, 2017, supported by a GMP certificate, a WHO-model Certificate of Pharmaceutical Product and the manufacturer's certificate of analysis¹³. In March 2026 PAHO asked countries to ensure "that the use of GLP-1 agonists is limited to indications approved by the national regulatory authority" and to strengthen pharmacovigilance, noting that the most frequent adverse events are gastrointestinal and usually temporary, with rarer pancreatitis, gallbladder disease and intestinal obstruction⁸. The trial results above apply to licensed products of known quality; they say nothing about products bought outside those channels⁸¹³.