Efficacy and Safety of Pioglitazone Monotherapy in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Abstract

Pioglitazone, the only thiazolidinedione drug in clinical practice is under scrutiny due to reported adverse effects, it’s unique insulin sensitising action provides rationale to remain as a therapeutic option for managing type 2 diabetes mellitus (T2DM). We conducted a systematic review and meta-analysis comparing pioglitazone monotherapy with monotherapies of other oral antidiabetic drugs for assessing its efficacy and safety in T2DM patients. Mean changes in glycated haemoglobin (HbA1c), and mean changes in fasting blood sugar (FBS) level, body weight (BW) and homeostasis model assessment-insulin resistance (HOMA-IR) were primary and secondary outcomes, respectively. Safety outcomes were changes in lipid parameters, blood pressure and incidences of adverse events. Metafor package of R software and RevMan software based on random-effects model were used for analyses. We included 16 randomised controlled trials. Pioglitazone monotherapy showed equivalent efficacy as comparators in reducing HbA1c by 0.05% (95% CI: −0.21 to 0.11) and greater efficacy in reducing FBS level by 0.24 mmol/l (95% CI: −0.48 to −0.01). Pioglitazone showed similar efficacy as comparators in reducing HOMA-IR (WMD: 0.05, 95% CI: −0.49 to 0.59) and increasing high-density lipoprotein level (WMD: 0.02 mmol/l, 95% CI: −0.06 to 0.10). Improved blood pressure (WMD: −1.05 mmHg, 95% CI: −4.29 to 2.19) and triglycerides level (WMD: −0.71 mmol/l, 95% CI: −1.70 to 0.28) were also observed with pioglitazone monotherapy. There was a significant association of pioglitazone with increased BW (WMD: 2.06 kg, 95% CI: 1.11 to 3.01) and risk of oedema (RR: 2.21, 95% CI: 1.48 to 3.31), though the risk of hypoglycaemia was absolutely lower (RR: 0.51, 95% CI: 0.33 to 0.80). Meta-analysis supported pioglitazone as an effective treatment option for T2DM patients to ameliorate hyperglycaemia, adverse lipid metabolism and blood pressure. Pioglitazone is suggested to prescribe following individual patient’s needs. It can be a choice of drug for insulin resistant T2DM patients having dyslipidaemia, hypertension or history of cardiovascular disease.

Pleural Effusion Due to Use of Pioglitazone: A Case Report

“…8 As all the other drugs, pioglitazone has some side effects that include edema, weight gain, bone loss, congestive heart failure, and the risk of bladder cancer. 9 It has been shown in a meta-analysis that pioglitazone monotherapy was significantly associated with risk of peripheral edema in type 2 DM patients. 9 The incidence of edema was higher, in particular among patients who were treated with oral hypoglycemic agents or insulin at baseline.…”

“…9 It has been shown in a meta-analysis that pioglitazone monotherapy was significantly associated with risk of peripheral edema in type 2 DM patients. 9 The incidence of edema was higher, in particular among patients who were treated with oral hypoglycemic agents or insulin at baseline. 3 Renal sodium retention 10 and vascular permeability 11 may contribute to pioglitazone-induced edema.…”

Gender differences in the efficacy of pioglitazone treatment in nonalcoholic fatty liver disease patients with abnormal glucose metabolism

“…Therefore, pioglitazone prescription should be avoided in patients with higher risk of heart failure. However, the potential risks do not appear to negate the bene cial effects and these side effects can be mitigated by optimizing dosing strategies and combining therapy with other medications in appropriate patients [11] .…”

Association between pioglitazone use and head and neck cancer: Population‐based case‐control study

“…Pioglitazone, an oral anti‐hyperglycemic agent used to treat type 2 diabetes mellitus (DM), was the 10th highest volume drug sold in the United States in 2008 . It belongs to the category of thiazolidinedione (TZD), which selectively stimulates the nuclear receptor, peroxisome proliferator‐activated receptor gamma (PPARγ) .…”

“…Pioglitazone, an oral anti‐hyperglycemic agent used to treat type 2 diabetes mellitus (DM), was the 10th highest volume drug sold in the United States in 2008 . It belongs to the category of thiazolidinedione (TZD), which selectively stimulates the nuclear receptor, peroxisome proliferator‐activated receptor gamma (PPARγ) . PPARγ, initially investigated for its role in adipocyte differentiation, has antiproliferative, proapoptotic, antiangiogenic, and anti‐inflammatory effects, which generated interest in exploring the potential of PPARγ agonists for aerodigestive cancer chemoprevention and treatment…”