Pioglitazone 15mg / Metformin 850mg tablets

This review evaluates the available pharmacokinetic data on the plasma-to-breastmilk transfer of first- and second-line T2DM drugs against available clinical guideline recommendations. A list of drug therapies for treating T2DM was generated from national and international clinical guidelines. A systematic search of research articles reporting human plasma and breastmilk drug concentrations was conducted in Scopus, PubMed, Google Scholar, and LactMed® in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies evaluating breastmilk drug transfer in T2DM, with fully accessible abstract and main text reported in English, were included. Study quality was evaluated using the ClinPK checklist. Authors evaluated clinical guideline recommendations on the use of T2DM drugs in lactation and the basis upon which such recommendations were made. Only 5 out of 20 drugs (metformin, glyburide, glipizide, tolbutamide, and semaglutide) have clinical data on plasma-to-breastmilk transfer. Metformin and tolbutamide were detectable in maternal plasma and breastmilk. Half (51.7%) of guideline recommendations provide explicit guidance. Only 4.4% of recommendations were based on clinical evidence. Over half (57.8%) of recommendations were accessible online, and most guideline recommendations (78%) were against the use of antiglycemic agents while breastfeeding. The scarce clinical evidence to guide T2DM drug therapy during breastfeeding available has several design and methodological limitations. Published recommendations remain largely inconsistent, thus perpetuating uncertainty in the use of T2DM drug therapies in lactation. Addressing knowledge gaps is critical in developing clinical consensus to optimize T2DM drug therapy among breastfeeding mothers.

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IntroductionAtherosclerotic cardiovascular disease (ASCVD) is a global concern, with diabetes being a key risk factor. Preventive measures increasingly rely on surrogate markers, such as carotid artery intima-media thickness (CIMT), a marker linked to ASCVD. Given the connection between dysglycaemia and ASCVD, the impact of oral hypoglycaemic agents (OHA) on CIMT is of interest. Despite the cardiovascular benefits of several OHAs, their effect on CIMT remains uncertain. This review aims to clarify the influence of OHAs on CIMT in patients with ASCVD and/or diabetes.ObjectivesThis systematic review aims to assess the effect of OHAs on CIMT in patients with ASCVD and/or diabetes mellitus (Type 1 or Type 2). We aim to provide evidence on the role of OHAs in reducing cardiovascular events in these high-risk patients.MethodologyA systematic search of databases, including Cochrane, Embase, CINAHL, Scopus and PubMed, was conducted to identify relevant randomised controlled trials (RCTs). We analysed the efficacy and adverse effects of OHAs on CIMT in adults with diabetes and/or cardiovascular disease.ResultsThe initial search identified 629 studies, with 13 selected, involving 3849 participants. Pioglitazone showed effectiveness in slowing CIMT progression in two out of three studies. Repaglinide was effective in reducing CIMT and inflammation, while Rosiglitazone showed no significant effect. Metformin, Sitagliptin and Alogliptin studies yielded mixed results, with some showing reduced CIMT progression but increased gastrointestinal and hypoglycaemia risks. SGLT-2 inhibitors Tofogliflozin and Ipragliflozin showed no significant CIMT reduction.ConclusionThe study suggests that prolonged use of Pioglitazone, Repaglinide and Alogliptin may significantly slow CIMT progression, improving cardiovascular risk management in patients with diabetes and/or cardiovascular disease. Further research is needed to understand the benefits and optimise oral hypoglycaemic treatment strategies for these patients.

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BackgroundAdolescents with polycystic ovary syndrome (PCOS) experience metabolic dysfunction, reproductive disturbance, and psychosocial burden. While combined hormonal contraceptives (CHC) are first-line pharmacologic treatment, concerns regarding side effects and long-term safety have spurred interest in nonhormonal alternatives. However, most evidence is derived from adult cohorts, leaving guidance specific to adolescents limited.Study objectivesTo systematically review the efficacy of nonhormonal pharmacotherapies including metformin, glucagon-like peptide-1 receptor agonists (GLP-1RAs), anti-androgens, and combination regimens in adolescents with PCOS.MethodsWe searched Medline, EMBASE, Cochrane Library, and CINAHL (1990-June 2025) for RCTs, cohort, and case-control studies enrolling PCOS teenagers aged 12-19 years. Two reviewers independently screened, extracted data, and assessed study quality. Outcomes included clinical signs (hirsutism, menstrual regularity), metabolic indices (BMI, insulin resistance, lipids), hormonal markers (testosterone, AMH), and patient-reported quality of life. This is the first systematic review on this topic.ResultsNineteen studies (744 adolescents) met the inclusion criteria: Eleven on metformin monotherapy, seven on SPIOMET (spironolactone, pioglitazone and metformin), and one on flutamide + metformin. Metformin alone modestly reduced BMI (1-2 kg/m² reduction), improved HOMA-IR (25% reduction), and restored menses in up to 91% of participants. SPIOMET improved ovulatory function and halved Ferriman-Gallwey scores, decreased visceral and hepatic fat, normalised inflammatory markers (CRP, GDF15), and sustained benefits up to one-year post-treatment, without significant weight change. Flutamide plus metformin yielded substantial anti-androgenic and metabolic improvements compared to CHCs. No full-text trials of GLP-1 receptor agonist monotherapy in adolescents were identified.ConclusionMetformin appears to have some benefits for adolescents with PCOS, offering some metabolic and menstrual benefits based on a small number of observational studies and small RCTs. SPIOMET and flutamide & metformin show superior, multi-domain efficacy but should be studied in larger RCTs. Critical gaps include adolescent-specific GLP-1RA data and standardized outcome measures to guide optimal nonhormonal strategies.

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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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