Pioglitazone 15mg / Metformin 850mg tablets

ABSTRACT Background Type 2 diabetes mellitus (T2DM) accounts for over 90% of diabetes cases worldwide. Pioglitazone, a thiazolidinedione, enhances insulin sensitivity by activating PPAR‐γ. Evidence on its efficacy and safety as an add‐on to metformin and SGLT2 inhibitors in inadequately controlled T2DM is limited. This systematic review and meta‐analysis evaluates pioglitazone's role as a third‐line therapy for improving glycaemic control in addition to metformin and Dapagliflozin. Methodology We conducted comprehensive searches across PubMed, CENTRAL, WOS, Scopus and EMBASE until December 2024. Pooled data were reported using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, along with a 95% confidence interval (CI). This systematic review and meta‐analysis is registered with PROSPERO ID: CRD42024612005 . Results We included three RCTs with 885 patients. Pioglitazone add‐on therapy significantly reduced HbA1c levels (MD: −0.41; 95% CI: −0.54 to −0.27, p = < 0.00001, I 2 = 0%), fasting blood glucose (MD: −11.91; 95% CI: −16.34 to −7.48, p = < 0.00001, I 2 = 0%), Homeostatic Model Assessment for Insulin Resistance (HOMA‐IR) (MD: −0.65; 95% CI: −1.05 to −0.25, p = 0.001, I 2 = 4.89%), increased the rate of achieving HbA1c < 7% (RR: 2.09; 95% CI: 1.66 to 2.64, p = < 0.00001, I 2 = 0%), and HbA1c < 6.5% (RR: 2.19; 95% CI: 1.36 to 3.53, p = 0.001, I 2 = 0%). However, there was no difference regarding Homeostasis model assessment of β‐cell function (HOMA‐β) between the two groups (MD: 2.73; 95% CI: −5.24 to 10.70, p = 0.5, I 2 = 27.53%). Conclusion Pioglitazone add‐on therapy significantly improved glycaemic control by reducing HbA1c, fasting blood glucose and HOMA‐IR while increasing the likelihood of achieving HbA1c targets. However, no significant difference was observed in HOMA‐β between groups. These findings suggest the potential benefit of pioglitazone in enhancing glycaemic outcomes in diabetes management.

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Alzheimer's disease (AD) and mild cognitive impairment (MCI) are major causes of cognitive decline. Antidiabetic medications such as metformin, pioglitazone, and GLP-1 receptor agonists have been proposed as potential neuroprotective therapies. We assessed whether these agents slow cognitive decline or disease progression in people with AD or MCI. PubMed, Embase, and Cochrane Central were searched for randomized controlled trials and observational studies of metformin, pioglitazone, or GLP-1 receptor agonists in AD/MCI. Results were synthesized narratively by drug class. Eleven studies met the inclusion criteria. Metformin, particularly in early-stage disease and metabolically vulnerable groups, demonstrated improvements in episodic memory and selective executive outcomes. Observational data in diabetic MCI suggested improved cognition and preservation of hippocampal and cortical structure, with limited amyloid-β and tau changes. Pioglitazone findings varied. Benefits were mainly reported in mild AD with type-2 diabetes, but not in non-diabetic AD/MCI. GLP-1 receptor agonists demonstrated preserved cerebral glucose metabolism and improved blood-to-brain glucose transport but did not improve cognitive function. Current evidence does not support antidiabetic therapies as effective treatments in AD/MCI. Any benefits appear to depend on disease stage and metabolic status, with metformin being the most promising candidate. Larger, longer-duration biomarker-defined trials are needed to determine whether any sustained clinical benefit is observed.

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AIM: To investigate the efficacy and safety of pioglitazone compared to placebo when added to metformin plus dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, for patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: In a multicentre study, with a randomized, double-blind, placebo-controlled design, 249 Korean patients with T2DM suboptimally managed on metformin and dapagliflozin were assigned to receive either pioglitazone (15 mg daily) or placebo for 24 weeks, followed by a 24-week pioglitazone extension. Primary outcomes included changes in glycated haemoglobin (HbA1c), with secondary outcomes assessing insulin resistance, adiponectin levels, lipid profiles, liver enzymes, body weight and waist circumference. RESULTS: Pioglitazone administration resulted in a significant reduction in HbA1c levels (from 7.80% ± 0.72% to 7.27% ± 0.82%) compared with placebo (from 7.79% ± 0.76% to 7.69% ± 0.86%, corrected mean difference: -0.42% ± 0.08%; p < 0.01) at 24 weeks. Additional benefits from pioglitazone treatment included enhanced insulin sensitivity, increased adiponectin levels, raised high-density lipoprotein cholesterol levels and reduced liver enzyme levels, resulting in improvement in nonalcoholic fatty liver disease liver fat score. Despite no serious adverse events in either group, pioglitazone therapy was modestly but significantly associated with weight gain and increased waist circumference. CONCLUSIONS: Adjunctive pioglitazone treatment in T2DM inadequately controlled with metformin and dapagliflozin demonstrates considerable glycaemic improvement, metabolic benefits, and a low risk of hypoglycaemia. These advantages must be weighed against the potential for weight gain and increased waist circumference.

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BACKGRUOUND: This study assessed the efficacy and safety of triple therapy with pioglitazone 15 mg add-on versus placebo in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and dapagliflozin. METHODS: In this multicenter, double-blind, randomized, phase 3 study, patients with T2DM with an inadequate response to treatment with metformin (≥1,000 mg/day) plus dapagliflozin (10 mg/day) were randomized to receive additional pioglitazone 15 mg/day (n=125) or placebo (n=125) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) levels from baseline to week 24 (ClinicalTrials.gov identifier: NCT05101135). RESULTS: At week 24, the adjusted mean change from baseline in HbA1c level compared with placebo was significantly greater with pioglitazone treatment (-0.47%; 95% confidence interval, -0.61 to -0.33; P<0.0001). A greater proportion of patients achieved HbA1c <7% or <6.5% at week 24 with pioglitazone compared to placebo as add-on to 10 mg dapagliflozin and metformin (56.8% vs. 28% for HbA1c <7%, and 23.2% vs. 9.6% for HbA1c <6.5%; P<0.0001 for all). The addition of pioglitazone also significantly improved triglyceride, highdensity lipoprotein cholesterol levels, and homeostatic model assessment of insulin resistance levels, while placebo did not. The incidence of treatment-emergent adverse events was similar between the groups, and the incidence of fluid retention-related side effects by pioglitazone was low (1.5%). CONCLUSION: Triple therapy with the addition of 15 mg/day of pioglitazone to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with T2DM inadequately controlled with dapagliflozin plus metformin.

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OBJECTIVE: To investigate the effects of metformin (MET) monotherapy and pioglitazone plus MET (PIOMET) therapy on gonadal and metabolic profiles in normal-weight women with polycystic ovary syndrome (PCOS). METHODS: Sixty normal-weight women with PCOS were recruited between January and September 2022 at the Shengjing Hospital of China Medical University. They were randomly assigned to the MET or PIOMET groups for 12 weeks of MET monotherapy or PIOMET therapy. Anthropometric measurements, menstrual cycle changes, gonadal profiles, and the oral glucose insulin-releasing test (OGIRT) were performed at baseline and after the 12-week treatment. RESULTS: Thirty-six participants completed the trial. MET and PIOMET therapies improved menstrual cycles after the 4- and 12-week treatments; however, there was no statistical difference between the two groups. PIOMET therapy improved luteinizing hormone (LH), luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, and free androgen index (FAI) levels after the 4-week treatment, whereas MET monotherapy only improved total testosterone (TT) levels compared to baseline (P < 0.05). Both MET and PIOMET therapies improved TT and anti-Mullerian hormone (AMH) levels after the 12-week treatment (P < 0.05). In addition, only PIOMET therapy significantly improved sex hormone-binding globulin (SHBG), FAI, and androstenedione (AND) levels than the baseline (P < 0.05). PIOMET therapy improved SHBG and AMH levels more effectively than MET monotherapy (P < 0.05). Furthermore, PIOMET treatment was more effective in improving blood glucose levels at 120 and 180 min of OGIRT compared to MET monotherapy (P < 0.05). CONCLUSIONS: In normal-weight women with PCOS, PIOMET treatment may have more benefits in improving SHBG, AMH, and postprandial glucose levels than MET monotherapy, and did not affect weight. However, the study findings need to be confirmed in PCOS study populations with larger sample sizes.

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INTRODUCTION: We aim to evaluate the efficacy and safety of pioglitazone/metformin fixed-dose combination (FDC) versus uptitrated metformin in patients with type 2 diabetes mellitus (T2DM) without adequate glycemic control. METHODS: A total of 304 patients were recruited from 15 hospitals in China and randomly assigned (1:1) to the test group (pioglitazone/metformin FDC, 15/500 mg) or the control group (uptitrated metformin, 2000-2500 mg/day). The primary endpoint was the proportion of patients with glycated hemoglobin A1c (HbA1c) ≤ 6.5% and ≤ 7.0% at week 16. The secondary outcomes included the change from baseline in glucose, serum lipids, and liver function. Full analysis set (FAS) and per-protocol set (PPS) were used for analyses. RESULTS: In the test group, 103 (69.59%) patients reached HbA1c ≤ 7.0% (FAS, P = 0.009), with 68 (45.95%) patients achieved HbA1c ≤ 6.5 (FAS, P = 0.043). More reduction in HbA1c, homeostatic model assessment for insulin resistance, and diastolic pressure was found. Bodyweight, body mass index, and high-density lipoprotein cholesterol increased markedly. The changes of triglycerides, alanine transaminase, aspartate aminotransferase, and high-sensitivity C-reactive protein decreased noticeably. There were no significant differences in rates of adverse events between the two groups. CONCLUSIONS: Pioglitazone/metformin FDC was superior to uptitrated metformin among patients with T2DM without adequate glycemic control. TRIAL REGISTRATION NUMBER: This trial is registered with the Chinese Clinical Trial Registry (ChiCTR1900028606).

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BACKGRUOUND: Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy. METHODS: The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety. RESULTS: After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were -1.38%±0.08%, -1.03%±0.08%, and -0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy. CONCLUSION: Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

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