The Evaluation of Risk Factors Associated with Adverse Drug Reactions by Metformin in Type 2 Diabetes Mellitus

Abstract

Metformin is a drug to improve glycemic control by reducing insulin resistance and is currently considered to be one of the first-choice drugs for type 2 diabetes mellitus (T2DM). However, during metformin use, adverse drug reactions (ADRs) including gastrointestinal adverse events were frequently observed. Thus, in the present study, we investigated the incidence of ADRs induced by metformin and further analyzed risk factors for ADRs in Japanese patients with type 2 diabetes mellitus who initially administered metformin (500-750 mg). One hundred and one hospitalized patients receiving metformin during September 1, 2009 and August 31, 2010 were studied. The incidence of ADRs and changes in laboratory data including hemoglobin A1c (HbA1c) were monitored retrospectively. The anti-glycemic effect of metformin was successfully observed as indicated by decreased HbA1c. Among ADRs, diarrhea was most frequently occurred during metformin use (26.7% of patients) although the symptom of diarrhea was mild in most cases and disappeared within 3 d after the initial use. A logistic regression analysis showed the existence of six risk factors, including initial dose (750 mg), female, age (≦65), body mass index (≧25), aspartate aminotransferase (≧30 IU/L) and alkaline phosphatase (≧270 IU/L). The incidence of diarrhea increased linearly as the number of risk factors increased. In conclusion, in order to avoid ADRs, especially diarrhea, subsequently improving the quality of life during metformin use, the optimization of the dose of metformin by considering risk factors would be beneficial for patients with T2DM.

Comparative effectiveness of metformin monotherapy in extended release and immediate release formulations for the treatment of type 2 diabetes in treatment‐naïve Chinese patients: Analysis of results from the CONSENT trial

“…Stratified randomization was used to minimize the impact of imbalanced factor distribution, which might influence study outcomes. Previous reports indicated that individuals with different body weights tend to have different GI conditions and differences in tolerability to metformin; however, the reported effect of BMI on GI tolerability is inconsistent . It is well known that baseline HbA1c level is positively correlated with the magnitude of HbA1c reduction from baseline with any oral hypoglycaemia medication …”

“…Previous reports indicated that individuals with different body weights tend to have different GI conditions and differences in tolerability to metformin; however, the reported effect of BMI on GI tolerability is inconsistent. 11,[19][20][21] It is well known that baseline HbA1c level is positively correlated with the magnitude of HbA1c reduction from baseline with any oral hypoglycaemia medication. 22 During the 16-week treatment period, metformin XR and IR were administered orally, with food, at a 500-mg/d starting dose.…”

Comparison of repaglinide and metformin monotherapy as an initial therapy in Chinese patients with newly diagnosed type 2 diabetes mellitus

“…Due to robust evidence, current international guidelines recommend metformin as the only first-line oral anti-hyperglycaemic agent for patients with newly diagnosed T2DM (7,18). As gastrointestinal complications occur in more than 20% of the patients using metformin (19,20), other anti-hyperglycaemic agents are considered as substitutes for the initial pharmacological therapy for those with contraindications to metformin. In this study, repaglinide and metformin had similar effects on HbA1c, which was in accordance with previous studies (10,11).…”

Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity

“…A daily oral dose of 2000–2500 mg/day is typically required for optimal effect8 and oral bioavailability is dose-dependent, with decreased bioavailability at higher doses, suggesting an active, saturable absorption process 9. Although severe adverse effects are rare, up to 30% of patients report gastrointestinal symptoms, including diarrhea, cramps, nausea, and vomiting, which can cause severe discomfort and lead to discontinuation of the drug 10. Therefore, finding strategies to reduce the dose of metformin required without compromising its efficacy is a useful approach for managing and reducing adverse events.…”