PepBloom

Semaglutide vs tirzepatide

What the research says about each, side by side. Every row comes from the studies and drug labels in the last row. More on each: Semaglutide and Tirzepatide.

SemaglutideTirzepatide
CategoryGLP-1 and metabolicGLP-1 and metabolic
EvidenceExtensive clinical researchExtensive clinical research
FDA statusFDA-approved as Ozempic (2017), Rybelsus (2019) and Wegovy (2021). Wegovy was also approved for lowering heart attack and stroke risk in 2024. Compounded copies aren't FDA-approved.FDA-approved as Mounjaro (2022, type 2 diabetes) and Zepbound (2023, weight management; 2024, sleep apnea with obesity). Compounded copies aren't FDA-approved.
How it worksIt switches on GLP-1 receptors in the pancreas, gut and brain. That helps the pancreas release insulin when blood sugar is high, slows how fast the stomach empties, and quiets hunger signals in the brain, so people feel full sooner and think about food less.The GLP-1 part lowers appetite, slows the stomach and helps insulin release. GIP is a second gut hormone that also boosts insulin after meals and seems to add to the effect on appetite and fat tissue. Hitting both receptors with one molecule gives more weight loss than GLP-1 alone in head-to-head trials.
Half-lifeAbout 7 days, so weekly shots build to a steady level after 4–5 weeks. Levels peak 1–3 days after a shot. The daily pill peaks about an hour after taking it.About 5 days. Levels peak 8–72 hours after a shot and reach a steady level after about 4 weeks of weekly shots.
Studied for
  • Type 2 diabetes blood sugar control
  • Weight management
  • Heart attack and stroke risk
  • Kidney disease in type 2 diabetes
  • Fatty liver disease (MASH)
  • Type 2 diabetes
  • Weight management
  • Obstructive sleep apnea
  • Heart failure with preserved ejection fraction
  • Fatty liver disease (MASH)
Reported side effects
  • Nausea, vomiting, diarrhea or constipation, mostly when the dose goes up
  • Gallbladder problems
  • Pancreatitis (rare)
  • Low blood sugar when combined with insulin or sulfonylureas
  • Boxed warning: thyroid C-cell tumors seen in rodents. Not for people with a personal or family history of medullary thyroid cancer or MEN 2.
  • Nausea, diarrhea, vomiting, constipation, indigestion, lower appetite
  • Can make birth-control pills less reliable for 4 weeks after starting and after each dose increase
  • Gallbladder problems and pancreatitis (rare)
  • Boxed warning: thyroid C-cell tumors seen in rodents. Not for people with a personal or family history of medullary thyroid cancer or MEN 2.
Sources
  1. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med, 2021 PubMed
  2. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med, 2023 PubMed
  3. Oral semaglutide in adults with overweight or obesity (OASIS 1). Lancet, 2023 PubMed
  4. Wegovy (semaglutide) prescribing information. DailyMed DailyMed
  5. Ozempic (semaglutide) prescribing information. DailyMed DailyMed
  1. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med, 2022 PubMed
  2. Tirzepatide monotherapy in type 2 diabetes (SURPASS-1). Lancet, 2021 PubMed
  3. Zepbound (tirzepatide) prescribing information. DailyMed DailyMed
  4. Mounjaro (tirzepatide) prescribing information. DailyMed DailyMed

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