Comparison of the effects of pioglitazone and metformin on hepatic and extra-hepatic insulin action in people with type 2 diabetes

Rita Basu, Pankaj Shah, Ananda Basu, Barbara Norby, Betty Dicke, Visvanathan Chandramouli, Ohad Cohen, Bernard R. Landau, Robert A. Rizza

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

OBJECTIVE - To determine mechanisms by which pioglitazone and metformin effect hepatic and extra-hepatic insulin action. RESEARCH DESIGN AND METHODS - Thirty-one subjects with type 2 diabetes were randomly assigned to pioglitazone (45 mg) or metformin (2,000 mg) for 4 months. RESULTS - Glucose was clamped before and after therapy at ∼5 mmol/l, insulin raised to ∼180 pmol/l, C-peptide suppressed with somatostatin, glucagon replaced at ∼75 pg/ml, and glycerol maintained at ∼200 mmol/l to ensure comparable and equal portal concentrations on all occasions. Insulin-induced stimulation of glucose disappearance did not differ before and after treatment with either pioglitazone (23 ± 3 vs. 24 ± 2 μmol · kg-1 · min-1) or metformin (22 ± 2 vs. 24 ± 3 μmol · kg-1 · min-1). In contrast, pioglitazone enhanced (P < 0.01) insulin-induced suppression of both glucose production (6.0 ± 1.0 vs. 0.2 ± 1.6 μmol · kg-1 · min-1) and gluconeogenesis (n = 11; 4.5 ± 0.9 vs. 0.8 ± 1.2 μmol · kg-1 · min-1). Metformin did not alter either suppression of glucose production (5.8 ± 1.0 vs. 5.0 ± 0.8 μmol · kg-1 · min-1) or gluconeogenesis (n = 9; 3.7 ± 0.8 vs. 2.6 ± 0.7 μmol · kg-1 · min-1). Insulin-induced suppression of free fatty acids was greater (P < 0.05) after treatment with pioglitazone (0.14 ± 0.03 vs. 0.06 ± 0.01 mmol/l) but unchanged with metformin (0.12 ± 0.03 vs. 0.15 ± 0.07 mmol/l). CONCLUSIONS - Thus, relative to metformin, pioglitazone improves hepatic insulin action in people with type 2 diabetes, partly by enhancing insulin-induced suppression of gluconeogenesis. On the other hand, both drugs have comparable effects on insulin-induced stimulation of glucose uptake.

Original languageEnglish (US)
Pages (from-to)24-31
Number of pages8
JournalDiabetes
Volume57
Issue number1
DOIs
StatePublished - Jan 2008

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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