Differential Impact of Metformin Combined with Sitagliptin or Pioglitazone on Glycemic Control and Adipokine Regulation in Type 2 Diabetes Mellitus

Section: Research Paper
Issue
Vol. 48 No. 1 (2026): Volume 48 Issue 1
Pages
10-16

Keywords:

Adiponectin, Leptin, Metformin, Pioglitazone, Sitagliptin

Abstract

Background: Type 2 diabetes mellitus (T2DM) involves insulin resistance and pancreatic β-cell dysfunction, with adipose tissue dysfunction playing a key role through imbalanced adipokines like leptin and adiponectin. The leptin-to-adiponectin ratio emerges as a sensitive marker of metabolic risk. While metformin is first-line therapy, combining it with sitagliptin or pioglitazone may differentially influence insulin sensitivity and adipokine profiles.


Aim: to assess how metformin plus sitagliptin and metformin plus pioglitazone affect adipokine levels, insulin resistance, and glycemic control in patients with T2DM.


Methods: This is a comparative observational study that enrolled 134 T2DM patients already stabilized on combination therapy for no more than 6 months including 68 on metformin 1000 mg/day + sitagliptin 50 mg twice daily; and 66 on metformin 1000 mg/day + pioglitazone 15 mg/day. Blood samples were collected after overnight fasting and were used to measure glucose, HbA1c, insulin, insulin resistance, pancreatic β-cell function, adiponectin, and leptin.


Results: The baseline characteristics of patients in both groups were not different significantly. The pioglitazone group showed lower fasting glucose (132.6±32.4 vs. 147.5±44.8 mg/dL, p=0.03), insulin (12.9±6.2 vs. 16.9±8.7 μU/mL, p=0.002), HOMA-IR (4.4±2.7 vs. 6.2±4.4, p=0.004), leptin (21.9±9.1 vs. 25.8±10.7 ng/mL, p=0.02), and LAR (4.3±2.3 vs. 5.2±2.5, p=0.03). LAR value is shown to be positively correlated with HOMA-IR in the studied groups (p<0.001).


Conclusion: In patients with T2DM, metformin plus pioglitazone was linked to a higher improvement in insulin sensitivity and adipokine balance than metformin plus sitagliptin. For determining the clinical significance of these differences, additional longitudinal studies evaluating cardiovascular outcomes are necessary, even though these findings point to a more favorable metabolic profile

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Authors

Israa O. Kashmoola

Nineveh Health Directorate, Mosul, Nineveh Province, 41006 and University of Mosul, College of Medicine, Department of Pharmacology, Mosul, Nineveh Province, 41002, Iraq

Shatha H. Mohammad

University of Mosul, College of Medicine, Department of Pharmacology, Mosul, Nineveh Province, 41002, Iraq

Mohammad H. Alsaaty

University of Mosul, College of Medicine, Department of Medicine, Mosul, Nineveh Province, 41002, Iraq

Identifiers

DOI: 10.33899/acmm.v48.i1.60386

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1.
Differential Impact of Metformin Combined with Sitagliptin or Pioglitazone on Glycemic Control and Adipokine Regulation in Type 2 Diabetes Mellitus. Ann. coll. Med. Mosul [Internet]. 2026 Jun. 29 [cited 2026 Jul. 18];48(1):10-6. Available from: https://mmed.uomosul.edu.iq/index.php/mmed/article/view/60386

How to Cite

1.
Differential Impact of Metformin Combined with Sitagliptin or Pioglitazone on Glycemic Control and Adipokine Regulation in Type 2 Diabetes Mellitus. Ann. coll. Med. Mosul [Internet]. 2026 Jun. 29 [cited 2026 Jul. 18];48(1):10-6. Available from: https://mmed.uomosul.edu.iq/index.php/mmed/article/view/60386