pioglitazone SR (AD-4833 SR) / Takeda, Zinfandel - LARVOL DELTA

RAMP: Response of Individuals With Ataxia-Telangiectasia to Metformin and Pioglitazone (clinicaltrials.gov) - P4; N=30; Not yet recruiting; Sponsor: NHS Tayside

New P4 trial • Biosimilar

The effect of pioglitazone and extended-release niacin on HDL-cholesterol in diabetes patients in a real-world setting (Int J Clin Pract) - P=NA, N=434; “…a statistically significant increase in HDL-C (+ 25.13%, p < 0.0001) was observed at the conclusion of combination therapy…Significant decreases in total cholesterol and triglycerides were detected, and HbA1c decreased 0.84% during combination therapy for all therapies combined.”

Clinical data • Atherosclerosis • Diabetes • Dyslipidemia

High-performance liquid chromatography quadrupole time-of-flight mass spectrometry method for the analysis of antidiabetic drugs in aqueous environmental samples (J Chromatogr B Analyt Technol Biomed Life Sci) - Mean recoveries of glibenclamide, vildagliptin, sitagliptin and pioglitazone in the matrices evaluated were in the range 78-83%; limits of quantification were in the range 0.4-4.3ngL(-1); and precision values were in the range 2.2-13%; Two of the antidiabetic drugs of recent prescription, sitagliptin and vildagliptin, were found in effluent wastewater at concentrations of 117ngL(-1) and 12ngL(-1), respectively, and in river water at concentrations of 35ngL(-1) and 6ngL(-1), respectively, whereas the classic antidiabetic drug glibenclamide and the novel drug pioglitazone were not detected

Analytical study • Diabetes

Revitalization of Pioglitazone: The Optimal Agent to be Combined with an SGLT2 Inhibitor. (PubMed) - Diabetes Obes Metab - "These observations suggest that pioglitazone might be an ideal agent to combine with empagliflozin to further reduce cardiovascular events in high risk diabetic individuals since empagliflozin also promotes salt/water loss and would be expected to offset any fluid retention associated with pioglitazone therapy. Herein, we provide an overview of the potential benefits of combined pioglitazone/empagliflozin therapy to prevent cardiovascular events in patients with type 2 diabetes mellitus."

Journal • Acute Coronary Syndrome • Biosimilar • Diabetes

Risks of cardiovascular diseases associated with dipeptidyl peptidase-4 inhibitors and other antidiabetic drugs in patients with type 2 diabetes: a nation-wide longitudinal study. (PubMed) - Cardiovasc Diabetol - "DPP4i-treated T2DM patients had lower risks for CVD as compared to those for non-DPP4i users, except metformin users."

Journal • Acute Coronary Syndrome • Biosimilar • Diabetes • Heart Failure • Reperfusion Injury

Advances in the treatment of type 2 diabetes: impact of dulaglutide. (PubMed) - Diabetes Metab Syndr Obes - "The most common adverse effects in clinical studies were gastrointestinal-related adverse events, and patient satisfaction was high with the use of dulaglutide. Dulaglutide is an appealing option for the treatment of type 2 diabetes, based on its once-weekly dosing, A1c lowering comparable to liraglutide, weight reduction comparable to exenatide, and a similar adverse-effect profile to other GLP-1 receptor agonists."

Journal • Review • Biosimilar • Diabetes

PPARγ Role in the Regulation of the TOMM40-APOE-C1 Genes Cluster (AAIC 2017) - "...Similar to the effect of PPARγ knockdown, the strongest response to Pioglitazone was also observed for APOE-mRNA, and another PPARγ agonist, Rosiglitazone (Rosi), produced results that were consistent with these... our results further established a role for PPARγ in regional transcriptional regulation of chr19q13.32, underpinning the association between PPARγ, the chr19q13.32 genes cluster, and human complex traits and disease including Alzheimer’s. The importance of our findings is enhanced in the context of the TOMMORROW study, a Phase III trial to evaluate pioglitazone on delay of onset of mild cognitive impairment (MCI), based on a genetics risk algorithm developed using the TOMM40 poly-T and APOE genotypes and age."

Biomarker • Alzheimer's Disease

The pharmacogenetics of type 2 diabetes: A systematic review (Diabetes Care) - N=7,279 Citations; “Significant medication-gene interactions for glycemic outcomes included 1) metformin and the SLC22A1, SLC22A2, SLC47A1, PRKAB2, PRKAA2, PRKAA1, and STK11 loci...repaglinide and the KCNJ11, SLC30A8, NEUROD1/BETA2, UCP2, and PAX4 loci; 4) pioglitazone and the PPARG2 and PTPRD loci; 5) rosiglitazone and the KCNQ1 and RBP4 loci...”

Biomarker • Review • Diabetes

Can Do Ramadan: Canagliflozin (Invokana™) vs. Standard Dual Therapy Regimen for T2DM During Ramadan (clinicaltrials.gov) - P4; N=116; Not yet recruiting; Sponsor: University of Leicester

New P4 trial • Biosimilar • Diabetes • Diabetic Nephropathy

Risk of Bias in Systematic Reviews of Non-Randomized Studies of Adverse Cardiovascular Effects of Thiazolidinediones and Cyclooxygenase-2 Inhibitors: Application of a New Cochrane Risk of Bias Tool. (PubMed) - PLoS Med - "The Cochrane RoB tool highlighted a wide range of risks of bias in studies included in two widely cited reviews and had the potential to change the conclusions of the reviews. Systematic reviews that incorporate non-randomized studies of medical interventions should include a detailed assessment of RoB for each included study."

Journal • Acute Coronary Syndrome • Biosimilar • Heart Failure

Effects of antidiabetic medications on the postprandial state in prediabetes (clinicaltrials.gov) - P4, N=50; Recruiting; New P4 trial.

New P4 trial • Diabetes • Obesity

A comparison of two treatment strategies in older participants with type 2 diabetes mellitus (T2DM) (IMPERIUM) (clinicaltrials.gov) - P4, N=880; Sponsor: Eli Lilly; Not yet recruiting -> Recruiting.

Enrollment open • Diabetes

Initial Combination Therapy with Metformin/Pioglitazone/Exenatide is More Effective Than Sequential Add-On Therapy in Subjects with New Onset Diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT):... (PubMed) - "Subjects receiving Triple Therapy experienced mean weight loss of 1.2kg versus mean weight gain of 4.1kg (p<0.01) with Conventional Therapy.` The results of this exploratory study demonstrate that combination therapy with metformin/pioglitazone/exenatide in newly diagnosed T2DM patients is more effective with less hypoglycemia than sequential add-on therapy with metformin, sulfonylurea, and then basal insulin."

Journal • Biosimilar • Diabetes • Obesity

Empagliflozin as Add-on Therapy to Pioglitazone With or Without Metformin in Patients With Type 2 Diabetes Mellitus. (PubMed) - "Empagliflozin 10 mg or 25 mg as add-on therapy to pioglitazone with or without metformin for 76 weeks was well tolerated and led to sustained reductions in HbA1c and weight compared with placebo in patients with type 2 diabetes. ClinicalTrials.gov identifier: NCT01210001."

Journal • Biosimilar • Diabetes • Immunology

Balaglitazone: A second generation peroxisome proliferator-activated receptor (PPAR) gamma (γ) agonist (Mini Rev Med Chem) - P3, N=409; Balaglitazone treated groups shown significantly reduce of HbA1c (%), FSG (mmol/L), postprandial glucose as comparison to pioglitazone; Drug provides robust glycemic control as an add-on to insulin therapy; Balaglitazone 10mg and 20mg show the similar magnitudes of the effects which comparable to the effects seen in the pioglitazone 45mg group

Review of P3 trials • Diabetes

CHMP recommends approval of Byetta for use with basal insulin (Amylin) - Amylin and Lilly announced that the CHMP of the European Medicines Agency (EMA) has issued a positive opinion in the EU for the expanded use of Byetta (exenatide twice-daily) as an add-on therapy to basal insulin, with or without metformin and/or Actos (pioglitazone), for the treatment of type 2 diabetes in adults who have not achieved adequate glycemic control with these agents

EMA positive recommendation • Diabetes

Initial triple combination therapy is more effective and safer than stepwise add on conventional therapy in newly diagnosed type 2 diabetes mellitus (EASD 2013) - Presentation time: Fri, Sep 27, 12:15 PM - 12:30 PM; Abstract #244; P=NA, N=144; NCT01107717; "...HbA1c declined to 6.3% at 6 mo and subsequently increased to 6.6% at mont 24. More subjects in the conventional arm failed to achieve the treatment HbA1c goal <6.5% (35 vs 16%, respectively, p<0.0001)."

Clinical data • Diabetes

Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): A 26-week double-blind study (Diabetes Care) - P3, N=822; DURATION-4; HbA(1c) reductions (%) at 26 weeks (least-squares means) with exenatide once weekly (EQW) vs MET, pioglitazone (PIO) and sitagliptin (SITA) were -1.53 vs. -1.48 (p=0.620), -1.63 (p=0.328), and -1.15 (p<0.001), respectively; Weight changes (kg) were -2.0 vs. -2.0 (p=0.892), +1.5 (p<0.001), and -0.8 (p<0.001), respectively; EQW was noninferior to MET but not PIO and superior to SITA with regard to HbA(1c) reduction at 26 weeks

P3 data • Diabetes

Exenatide Extended-Release: An Updated Review of Its Use in Type 2 Diabetes Mellitus. (PubMed) - "Thus, exenatide ER is a useful treatment option in the management of type 2 diabetes. It offers a convenient, once-weekly regimen and can be administered by patients via a pen injection system or syringes and needles."

Journal • Biosimilar • Diabetes

A phase III study of BMS-512148 (dapagliflozin) in Asian patients with type 2 diabetes who are not well controlled on metformin alone (clinicaltrials.gov) - P3, N=444; Recruiting -> Active, not recruiting; Start date: Jun 2010 -> Jan 2010

Enrollment closed • Start date • Diabetes

Efficacy and tolerability of the DPP-4 inhibitor alogliptin combined with pioglitazone, in metformin-treated patients with type 2 diabetes (J Clin Endocrinol Metab) - P3, N=1,554; U1111-1113-8587; When added to metformin, the least squares mean change (LSMΔ) from baseline HbA(1c) was -0.9 ± 0.05% in the Pio-alone group and -1.4 ± 0.05% in both the A12.5+P and A25+P groups (p< 0.001 for both comparisons); A12.5+P and A25+P produced greater reductions in fasting plasma glucose (LSMΔ=-2.5 ± 0.1 mmol/liter for both) than Pio alone (LSMΔ=-1.6 ± 0.1 mmol/liter; p<0.001); A12.5+P and A25+P significantly improved measures of β-cell function (proinsulin:insulin and homeostasis model assessment of β-cell function) compared to Pio alone, but had no effect on homeostasis model assessment of insulin resistance

P3 data • Diabetes

Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: A randomised double-blind placebo-controlled study (Diabetologia) - P3, N=71; SYR-322_301; At week 16, Alo (n=25) and Alo/Pio (n=21) vs Pbo (n=24) produced similar significant reductions in total postprandial TG response (incremental AUC [iAUC]; p<0.001), as well as in chylomicron TG (p<0.001) and VLDL1 TG iAUCs (p<0.001 and p=0.012, respectively); Postprandial chylomicron apolipoprotein B-48 iAUC showed a significant decrease after Alo treatment (p=0.028), and a non-significant trend towards a decrease with Alo/Pio (p=0.213)

P3 data • Diabetes

Efficacy and safety of lixisenatide once daily versus placebo in patients with type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P) (ADA 2012) - Presentation time: 6/9/2012 11:30:00 AM; NCT00763815; P3, N=484; Lixisenatide QD produced significantly greater HbA1c reduction vs placebo and a greater proportion of patients achieved HbA1c <7.0% (52% lixisenatide vs 26% placebo; p<0.0001) & well tolerated, with a similar proportion of AEs and serious AEs (72.4% and 2.5% in the lixisenatide group vs 72.7% and 1.9% in the placebo group)

P3 data • Diabetes

Risk of bladder cancer in diabetic patients treated with rosiglitazone or pioglitazone: A nested case-control study (Drug Saf) - PMID: 23797604; N=3,412 cases of newly diagnosed bladder cancer and 17,060 controls; "Long-term exposures to pioglitazone and rosiglitazone were associated with higher odds of bladder cancer, and the highest odds were seen in users with ≥2 years of exposure"

Retrospective data • Diabetes

A review on thiazolidinediones and bladder cancer in human studies (J Environ Sci Health C Environ Carcinog Ecotoxicol Rev) - "These studies showed a signal of higher risk of bladder cancer associated with pioglitazone, especially at a higher cumulative dose or after prolonged exposure; however, a weaker signal or null association is observed with rosiglitazone."

Adverse events • Review • Diabetes