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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
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Oral Hypoglycemic Agents: Glinides01:06

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Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
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α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
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Prokinetic agents are specialized medications that stimulate gastrointestinal (GI) motility, promoting food movement through the GI tract. Dopamine, an inhibitory neurotransmitter, plays a significant role in this process, reducing GI motility and indirectly controlling the speed of digestion. Dopamine receptor antagonists, such as metoclopramide and domperidone, offer a unique advantage as prokinetic agents. By blocking the dopamine receptors, these drugs increase GI motility, improving food...
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Gastric Neoplasm Risk with DPP-4 Inhibitors, GLP-1 Receptor Agonists, and SGLT2 Inhibitors: Network Meta-Analysis of

Chao-Ming Hung1,2, Chih-Wei Hsu3, Bing-Syuan Zeng4

  • 1Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan.

International Journal of Molecular Sciences
|March 28, 2026
PubMed
Summary
This summary is machine-generated.

Newer glucose-lowering therapies show varied gastric neoplasm risks. Glucagon-like peptide-1 receptor agonists (GLP1RAs) may lower risk, while dipeptidyl peptidase-4 inhibitors (DPP4is) might increase it, especially in longer-term diabetes treatment.

Keywords:
DPP-4 inhibitorGLP-1 receptor agonistSGLT2 inhibitordiabetes mellitusgastric neoplasmssemaglutide

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Area of Science:

  • Endocrinology
  • Gastroenterology
  • Pharmacovigilance

Background:

  • The safety of newer glucose-lowering therapies, including DPP4is, GLP1RAs, and SGLT2is, regarding gastric neoplasm risk is uncertain.
  • Global use and long-term application in predisposed populations necessitate comparative safety data.

Purpose of the Study:

  • To systematically review and network meta-analyze randomized controlled trials (RCTs) evaluating the risk of gastric neoplasms associated with DPP4is, GLP1RAs, and SGLT2is.
  • To provide decision-grade comparative safety evidence for these widely used diabetes medications.

Main Methods:

  • Systematic review and random-effects frequentist network meta-analysis (NMA) of RCTs in adults without baseline gastric neoplasms.
  • Searched multiple databases (PubMed, Embase, etc.) from inception to January 2026.
  • Assessed certainty of evidence using GRADE adapted for NMA.

Main Results:

  • GLP1RAs were associated with a lower risk of gastric neoplasms compared to controls (RR = 0.51).
  • DPP4is were associated with a higher risk of gastric neoplasms compared to controls (RR = 1.77).
  • These associations persisted in subgroups with diabetes, longer trial durations (≥52 weeks), and older populations (age ≥60 years).

Conclusions:

  • GLP1RA use appears to have a relatively lower gastric neoplasm risk than controls.
  • DPP4is warrant heightened vigilance and mechanistic investigation due to increased risk, particularly in patients with diabetes on long-term therapy.
  • Findings suggest improved neoplasm ascertainment in future trials rather than immediate prescribing changes.