Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity
Although tirzepatide and semaglutide were shown to reduce weight in randomized clinical trials, data from head-to-head comparisons in populations with overweight or obesity are not yet available.
Rodriguez PJ, Goodwin Cartwright BM, Gratzl S et al. — JAMA internal medicine
Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity
Oral semaglutide at a dose of 25 mg may provide an alternative treatment option to injectable semaglutide (2.4 mg) and higher-dose oral semaglutide (50 mg) for persons with overweight or obesity.
Wharton S, Lingvay I, Bogdanski P et al. — The New England journal of medicine
Tirzepatide as Compared with Semaglutide for the Treatment of Obesity
Tirzepatide and semaglutide are highly effective medications for obesity management. The efficacy and safety of tirzepatide as compared with semaglutide in adults with obesity but without type 2 diabetes is unknown.
Aronne LJ, Horn DB, le Roux CW et al. — The New England journal of medicine
Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes
Tirzepatide, a dual incretin agonist of the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors, has favorable effects on glycemic control and body weight. The effects on cardiovascular outcomes are uncertain.
Nicholls SJ, Pavo I, Bhatt DL et al. — The New England journal of medicine
Mechanisms of GLP-1 Receptor Agonist-Induced Weight Loss: A Review of Central and Peripheral Pathways in Appetite and Energy Regulation
Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have become central in managing obesity and type 2 diabetes, primarily through appetite suppression and metabolic regulation. This review explores the mechanisms underlying GLP-1 RA-induced w...
Moiz A, Filion KB, Tsoukas MA et al. — The American journal of medicine
Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis
Weight reduction has been shown to alleviate symptoms of osteoarthritis of the knee, including pain. The effect of glucagon-like peptide-1 receptor agonists on outcomes in knee osteoarthritis among persons with obesity has not been well studied.
Bliddal H, Bays H, Czernichow S et al. — The New England journal of medicine
Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial
In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified ana...
Ryan DH, Lingvay I, Deanfield J et al. — Nature medicine
Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial
The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown.
Aronne LJ, Sattar N, Horn DB et al. — JAMA
Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis
Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease associated with liver-related complications and death. The efficacy and safety of tirzepatide, an agonist of the glucose-dependent insulinotropic polypeptide an...
Loomba R, Hartman ML, Lawitz EJ et al. — The New England journal of medicine
Tirzepatide for overweight and obesity management
Tirzepatide is a once-weekly dual agonist, acting on glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. It is approved at the same doses (5, 10 and 15 mg) for both type 2 diabetes (T2D) and chr...
Hamza M, Papamargaritis D, Davies MJ — Expert opinion on pharmacotherapy
GLP-1 physiology in obesity and development of incretin-based drugs for chronic weight management
The introduction of the highly potent incretin receptor agonists semaglutide and tirzepatide has marked a new era in the treatment of type 2 diabetes and obesity. With normalisation of glycated haemoglobin levels and weight losses around 15-25%, t...
Holst JJ — Nature metabolism
Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics
Tirzepatide, a once-weekly GIP/GLP-1 receptor agonist, reduces blood glucose and body weight in people with type 2 diabetes. The cardiovascular (CV) safety and efficacy of tirzepatide have not been definitively assessed in a cardiovascular outcome...
Nicholls SJ, Bhatt DL, Buse JB et al. — American heart journal
GLP-1 Agonists for Weight Loss: Pharmacology and Clinical Implications
This review investigates the various pharmacologic treatments for overweight and obesity in adults, especially glucagon-like peptide 1 (GLP-1) agonists. In light of the globally expanding obesity pandemic and the limited selection of treatmen...
Moore PW, Malone K, VanValkenburg D et al. — Advances in therapy
Incretin hormones and type 2 diabetes
Incretin hormones (glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide-1 [GLP-1]) play a role in the pathophysiology of type 2 diabetes. Along with their derivatives they have shown therapeutic success in type 2 diabetes, ...
Nauck MA, Müller TD — Diabetologia
Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials
Obesity is a chronic disease with high prevalence and associated comorbidities, making it a growing global concern. These comorbidities include type 2 diabetes, hypertension, ventilatory dysfunction, arthrosis, venous and lymphatic circulation dis...
Popoviciu MS, Păduraru L, Yahya G et al. — International journal of molecular sciences
Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial
The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-relat...
Garvey WT, Batterham RL, Bhatta M et al. — Nature medicine
Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial
Phase 3 trials have not compared semaglutide and liraglutide, glucagon-like peptide-1 analogues available for weight management.
Rubino DM, Greenway FL, Khalid U et al. — JAMA
Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes: A Systematic Review and Meta-Analysis
The weight loss benefit of semaglutide in patients with diabetes is well-documented, but its clinical utility in treating obesity among patients without diabetes is less described. We therefore assessed the efficacy and safety of subcutaneous sema...
Tan HC, Dampil OA, Marquez MM — Journal of the ASEAN Federation of Endocrine Societies
Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension
To explore changes in body weight and cardiometabolic risk factors after treatment withdrawal in the STEP 1 trial extension.
Wilding JPH, Batterham RL, Davies M et al. — Diabetes, obesity & metabolism
Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial
The effects of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, as an addition to insulin glargine for treatment of type 2 diabetes have not been described.
Dahl D, Onishi Y, Norwood P et al. — JAMA
Tirzepatide: A Systematic Update
Tirzepatide is a new molecule capable of controlling glucose blood levels by combining the dual agonism of Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) receptors. GIP and GLP1 are incretin hormones: they a...
Forzano I, Varzideh F, Avvisato R et al. — International journal of molecular sciences
GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects
Glucagon like peptide-1 (GLP-1) is an incretin secretory molecule. GLP-1 receptor agonists (GLP-1RAs) are widely used in the treatment of type 2 diabetes (T2DM) due to their attributes such as body weight loss, protection of islet β cells, p...
Zhao X, Wang M, Wen Z et al. — Frontiers in endocrinology
Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial
This trial assessed the efficacy and safety of the GLP-1 analogue once a week subcutaneous semaglutide 2·4 mg versus semaglutide 1·0 mg (the dose approved for diabetes treatment) and placebo for weight management in adults with overweigh...
Davies M, Færch L, Jeppesen OK et al. — Lancet (London, England)
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial
The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown.
Rubino D, Abrahamsson N, Davies M et al. — JAMA
Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial
Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches.
Wadden TA, Bailey TS, Billings LK et al. — JAMA
Once-Weekly Semaglutide in Adults with Overweight or Obesity
Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.
Wilding JPH, Batterham RL, Calanna S et al. — The New England journal of medicine
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes
Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared ...
Frías JP, Davies MJ, Rosenstock J et al. — The New England journal of medicine
Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial
Despite advancements in care, many people with type 2 diabetes do not meet treatment goals; thus, development of new therapies is needed. We aimed to assess efficacy, safety, and tolerability of novel dual glucose-dependent insulinotropic polypept...
Rosenstock J, Wysham C, Frías JP et al. — Lancet (London, England)
Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist
Tirzepatide (LY3298176) is a dual GIP and GLP-1 receptor agonist under development for the treatment of type 2 diabetes mellitus (T2DM), obesity, and nonalcoholic steatohepatitis. Early phase trials in T2DM indicate that tirzepatide improves clini...
Willard FS, Douros JD, Gabe MB et al. — JCI insight
The Discovery and Development of Liraglutide and Semaglutide
The discovery of glucagon-like peptide-1 (GLP-1), an incretin hormone with important effects on glycemic control and body weight regulation, led to efforts to extend its half-life and make it therapeutically effective in people with type 2 diabete...
Knudsen LB, Lau J — Frontiers in endocrinology
Glucagon-like peptide 1 (GLP-1)
The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition ...
Müller TD, Finan B, Bloom SR et al. — Molecular metabolism
GLP-1: Molecular mechanisms and outcomes of a complex signaling system
Meal ingestion provokes the release of hormones and transmitters, which in turn regulate energy homeostasis and feeding behavior. One such hormone, glucagon-like peptide-1 (GLP-1), has received significant attention in the treatment of obesity and...
Smith NK, Hackett TA, Galli A et al. — Neurochemistry international
Incretin hormones: Their role in health and disease
Incretin hormones are gut peptides that are secreted after nutrient intake and stimulate insulin secretion together with hyperglycaemia. GIP (glucose-dependent insulinotropic polypeptide) und GLP-1 (glucagon-like peptide-1) are the known incretin ...
Nauck MA, Meier JJ — Diabetes, obesity & metabolism
Biology of incretins: GLP-1 and GIP
This review focuses on the mechanisms regulating the synthesis, secretion, biological actions, and therapeutic relevance of the incretin peptides glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The published...
Baggio LL, Drucker DJ — Gastroenterology