Gastrointestinal tolerability of extended-release metformin tablets compared to immediate-release metformin tablets: results of a retrospective cohort study

Curr Med Res Opin. 2004 Apr;20(4):565-72. doi: 10.1185/030079904125003278.


Objective: Metformin, a biguanide antihyperglycemic medication, lowers blood glucose in patients with type 2 diabetes with minimal risk of hypoglycemia. Most common side effects include diarrhea, nausea and vomiting. Extended-release metformin (Glucophage XR)*, a once-daily tablet using the patented GelShield Diffusion System release mechanism, may be better tolerated than immediate-release metformin (Glucophage). This retrospective chart review examined the overall gastrointestinal (GI) tolerability of both formulations.

Research design and methods: Patient charts were reviewed and data were collected from October 2001 to May 2002. Adult patients with type 2 diabetes started on extended-release metformin (metformin-XR) or switched from immediate-release metformin to metformin-XR within the previous 2 years were eligible for inclusion in the metformin-XR cohort. Patients started on immediate-release metformin within the previous 2 years were eligible for inclusion in the immediate-release metformin cohort. Previous experience of GI side effects while taking immediate-release metformin did not prevent inclusion in either cohort, though patients with significant underlying GI disease or moderate to severe hepatic or renal impairment were excluded. GI tolerability was assessed during the first year of treatment with immediate-release metformin or metformin-XR. Primary endpoints were overall GI tolerability and frequency of diarrhea during the first year of treatment.

Results: A total of 471 patients' charts were reviewed and data were collected from four diabetes clinics; 310 (metformin-XR) and 158 (immediate-release metformin) eligible patients were included. Patients were, on average, 56 years old, and overweight (mean body mass index 33 kg/m2). The majority of patients were Caucasian (50%), Hispanic (24%) or Black (19%). Mean daily doses were 1258 mg (range 500-2500 mg) for metformin-XR and 1282 mg (range 500-2550 mg) for immediate-release metformin. About 25% of the metformin-XR cohort had been switched from immediate-release metformin due to a history of GI adverse events (AE). Despite this, the frequency of any GI AE was similar between metformin-XR and immediate release metformin (11.94 vs. 11.39%, p = 0.86). The incidence of individual GI AE also did not differ significantly between cohorts. In a cohort of 205 patients started on immediate-release metformin and switched to metformin-XR, the frequency of any GI AE was 26.34% (while taking immediate release metformin; n = 205) vs. 11.71% (after switching to metformin-XR; n = 205) (p = 0.0006) and the frequency of diarrhea was 18.05% (while taking immediate-release metformin) vs. 8.29% (after switching to metformin-XR) (p = 0.0084).

Conclusions: In this retrospective chart review, patients switched from immediate-release metformin to metformin-XR experienced fewer GI side effects on comparable doses of the extended-release metformin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Delayed-Action Preparations
  • Female
  • Gastrointestinal Diseases / chemically induced*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Male
  • Metformin / administration & dosage
  • Metformin / adverse effects*
  • Middle Aged
  • Retrospective Studies
  • Tablets


  • Delayed-Action Preparations
  • Hypoglycemic Agents
  • Tablets
  • Metformin