Can metformin cause stomach ulcers
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Can Metformin Cause Stomach Ulcers?
Introduction to Metformin and Gastrointestinal Effects
Metformin is a widely used medication for the treatment of type 2 diabetes mellitus. While it is effective in managing blood glucose levels, its administration is often associated with gastrointestinal adverse events. These include abdominal pain, diarrhea, and nausea, which can limit its use in some patients6. However, the question remains whether metformin can cause more severe gastrointestinal issues, such as stomach ulcers.
Metformin's Gastroprotective Properties
Healing Effects on Indomethacin-Induced Gastric Ulcers
Research has shown that metformin may actually have protective effects against gastric ulcers. In a study involving rats, metformin was found to decrease stomach acidity and ulcer index, restore histological features, and increase mucin levels. These effects were comparable to those of omeprazole, a well-known ulcer treatment. The study suggested that metformin's anti-inflammatory activity and its ability to increase nitric oxide levels contribute to its ulcer-healing properties1.
Protection Against Alendronate-Induced Gastric Damage
Another study evaluated the gastroprotective activity of metformin in rats with alendronate-induced gastric damage. The results indicated that metformin significantly reduced the inflammatory response and maintained basal levels of collagen and mucus production. This gastroprotective effect was linked to the activation of the AMPK pathway, suggesting that metformin could be a potential therapeutic agent for preventing and treating gastric lesions2.
Effects on Ethanol- and Indomethacin-Induced Gastric Ulcers
Further research demonstrated that metformin decreased the extent of gastric lesions in both ethanol and indomethacin-induced ulcer models. The study highlighted metformin's antioxidant and anti-apoptotic properties, as well as its ability to restore blood flow, as key factors in its gastroprotective effects4.
Metformin and Stomach Cancer Risk
Interestingly, a retrospective study in Korea found that metformin use was associated with a reduced risk of stomach cancer in diabetic patients. The study analyzed data from the National Health Insurance Service-National Health Screening Cohort and found that metformin users had a lower incidence of stomach cancer compared to non-users. This suggests that metformin may have protective effects against more severe gastrointestinal conditions7.
Conclusion
While metformin is associated with some gastrointestinal side effects such as abdominal pain, diarrhea, and nausea, current research indicates that it does not cause stomach ulcers. On the contrary, metformin appears to have gastroprotective properties, reducing the risk and severity of gastric ulcers and potentially lowering the risk of stomach cancer. These findings highlight the multifaceted benefits of metformin beyond its primary use in diabetes management.
Sources and full results
Most relevant research papers on this topic
The Effect of Metformin on Indomethacin-induced Gastric Ulcer: Involvement of Nitric oxide/Rho kinase pathway.
Metformin has comparable ulcer healing effects to omeprazole, partly due to its anti-inflammatory activity and increasing nitric oxide levels.
Non-RCT
Animal Study
Rigorous JournalAlendronate-induced gastric damage in normoglycemic and hyperglycemic rats is reversed by metformin.
Metformin has a gastroprotective effect in alendronate-induced gastric damage, potentially due to its activation of the AMPK pathway.
Non-RCTAnimal StudyRigorous JournalGastroprotective effects of the insulin sensitizers rosiglitazone and metformin against indomethacin‐induced gastric ulcers in Type 2 diabetic rats
Rosiglitazone and metformin show gastroprotective effects against indomethacin-induced gastric ulcers in Type 2 diabetic rats, suggesting potential benefits for patients with this condition.
Non-RCTAnimal StudyThe Effect of Metformin on Ethanol- and Indomethacin-Induced Gastric Ulcers in Rats
Metformin effectively reduces gastric ulcer development in non-diabetic, non-hyperglycemic rats due to its antioxidant and anti-apoptotic properties, as well as its ability to restore blood flow.
Metformin maintains mucosal integrity in experimental model of colitis by inhibiting oxidative stress and pro-inflammatory signaling.
Metformin effectively maintains colonic mucosal integrity and reduces inflammation in a rat model of colitis by inhibiting oxidative stress and pro-inflammatory signaling.
RCTAnimal StudyRigorous JournalGastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials
Metformin use is associated with a higher risk of gastrointestinal adverse events like abdominal pain, nausea, and diarrhea, with a higher risk of bloating and diarrhea with immediate-release formulations compared to extended-release formulations.
Meta-AnalysisMetformin use reduced the risk of stomach cancer in diabetic patients in Korea: an analysis of Korean NHIS-HEALS database
Metformin use in diabetic patients in Korea reduces the risk of stomach cancer incidence.
Observational StudyRigorous JournalRevisiting metformin therapy for the mitigation of diabetic foot ulcer in patients with diabetic kidney disease from real‐world evidence
Metformin therapy in patients with diabetic kidney disease can lower diabetic foot ulcer incidence and progression.
Observational StudyMetformin Therapy and Risk of Cancer in Patients with Type 2 Diabetes: Systematic Review
Metformin may be associated with a significant reduction in the risk of cancer and cancer-related mortality in patients with type 2 diabetes.
Systematic ReviewRigorous Journal
Highly CitedGut microbiota is correlated with gastrointestinal adverse events of metformin in patients with type 2 diabetes
Metformin increases gut hormone secretion by increasing short-chain fatty acid-producing bacteria, which may cause gastrointestinal adverse events in patients with type 2 diabetes.
RCTAnimal Study