Juvisync (sitagliptin/simvastatin) / Merck (MSD) - LARVOL DELTA

Comparative efficacy of adjuvant drugs in improving IVF/ICSI outcomes and reducing ovarian hyperstimulation syndrome in women with polycystic ovary syndrome: a systematic review and network meta-analysis (ISGE 2024) - "Randomized controlled trials (RCTs) that investigated adjuvant drugs, including metformin, pioglitazone, simvastatin, sitagliptin, myoinositol/inositol, L-carnitine, N-acetyl-cysteine (NAC), and combination treatment, in PCOS patients were included, with placebo or no adjuvant treatment as the control. In total, 21 RCTs were included, with 1749 patients randomized to 9 adjuvant drugs. Both pairwise meta-analysis and network meta-analysis indicated that all adjuvant drugs presented no significant difference in improving clinical pregnancy. Network meta-analysis showed that myoinositol [odds ratio (OR)=0.17, 95% confidence interval (CI) 0.04-0.72] and metformin (OR=0.47, 95% CI 0.27-0.82) may be associated with lower risk of ovarian hyperstimulation syndrome (OHSS) than the control group."

Retrospective data • Review • Gynecology • Polycystic Ovary Syndrome

Genotoxic and cytotoxic assessment of sitagliptin and simvastatin alone and in combination. (PubMed, Pak J Pharm Sci) - "The genotoxic assay spotted that Simvastatin produced less damage to DNA with the threshold of 500μg/ml whereas Sitagliptin significantly damage above the 250μg/mL, However, combination of drugs produced lesser damage than Sitagliptin alone. The findings concluded a non-genotoxic combination of sitagliptin and simvastatin which possess a least cytotoxic potential suggesting the safe use of the combination both in T2DM and CHD."

Journal • Cardiovascular • Coronary Artery Disease • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus

Oral anti-diabetic drugs as endocrine disruptors in vitro - No evidence for additive effects in binary mixtures. (PubMed, Toxicol In Vitro) - "The in vitro H295R steroidogenesis assay was implemented to investigate endocrine effects of three ADDs, metformin (MET), glimepiride (GLIM), sitagliptin (SIT) and the cholesterol-lowering drug simvastatin (SIM) individually and in three binary mixtures...The complexity of dynamic pathways such as steroidogenesis appears to significantly reduce the use of the CA model. In conclusion, more dynamic models are needed to predict mixture effects in complex systems."

Journal • Preclinical • Diabetes • Metabolic Disorders

Assessment of the Drug Interaction Potential of Ertugliflozin With Sitagliptin, Metformin, Glimepiride, or Simvastatin in Healthy Subjects. (PubMed, Clin Pharmacol Drug Dev) - "All treatments were well tolerated. The lack of clinically meaningful pharmacokinetic interactions demonstrates that ertugliflozin can be coadministered safely with sitagliptin, metformin, glimepiride, or simvastatin without any need for dose adjustment."

Clinical • Journal • Diabetes • Type 2 Diabetes Mellitus

Epidemiology of Acute Pancreatitis in Southern Israel: A Retrospective Study. (PubMed, Isr Med Assoc J) - "Biliary pancreatitis is the main cause of acute pancreatitis in southern Israel, similar to the rest of the world, and constitutes a much more common etiology than alcohol. Furthermore, drug-induced pancreatitis is a common etiology, with disothiazide being the most common drug associated with pancreatitis followed by ACE-Inhibitors, sitagliptin, and simvastatin. Recurrence of pancreatitis is common in this geographic area, and older age, advanced CTSI grading, bilateral pleural effusion, and being single are all poor prognostic predictive factors."

Journal • Retrospective data • Dyslipidemia • Hypertriglyceridemia • Immunology • Pancreatitis

Phase shift: Combination product in development --> Under review (Merck (MSD)) - MK- 0431D/ Merck

Corporate Pipeline Update

A study of the efficacy and safety of MK-0431D (a fixed-dose combination of sitagliptin and simvastatin) for the treatment of patients with type 2 diabetes mellitus (T2DM) with inadequate glycemic control on metformin monotherapy (MK-0431D-266) (clinicaltrials.gov) - P3, N=750; Sponsor: Merck; Not yet recruiting -> Recruiting

Enrollment open • Diabetes

FDA approves Merck's JUVISYNC (sitagliptin and simvastatin) tablets, a once-daily therapy for patients with type 2 diabetes who need to lower blood sugar and cholesterol, known risk factors for cardiovascular disease (Merck (MSD)) - FDA has approved Merck 's JUVISYNC (sitagliptin and simvastatin), a new treatment for T2D that combines sitagliptin, with the cholesterol-lowering medication ZOCOR (simvastatin); JUVISYNC is first treatment option for healthcare providers to help patients who need blood sugar-lowering benefits of a DPP-4 inhibitor and cholesterol-lowering benefits of simvastatin, with convenience of a single tablet once daily

FDA approval • Diabetes

Overview of the Clinical Pharmacology of Ertugliflozin, a Novel Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor. (PubMed, Clin Pharmacokinet) - "Concomitant administration of metformin, sitagliptin, glimepiride, or simvastatin with ertugliflozin did not have clinically meaningful effects on the PK of ertugliflozin or the coadministered medications. Coadministration of rifampin decreased ertugliflozin AUC and C by 39% and 15%, respectively, and is not expected to affect efficacy in a clinically meaningful manner. This comprehensive evaluation supports administration to patients with T2DM without regard to prandial status and with no dose adjustments for coadministration with commonly prescribed drugs, or in patients with renal impairment or mild-to-moderate hepatic impairment based on ertugliflozin PK."

Clinical • Journal • Review • Diabetes • Metabolic Disorders • Renal Disease • Type 2 Diabetes Mellitus

Vascular AMPK: enhancer, brake or both? (PubMed, Basic Clin Pharmacol Toxicol) - "The vascular protective effects of certain antidiabetic (metformin and sitagliptin) or lipid-lowering (simvastatin and fenofibrate) therapeutic agents, of active components of Chinese medicinal herbs (resveratrol and berberine), and of pharmacological agents (AICAR, A769662 and PT1) have been attributed to the activation of AMPK (in endothelial cells, vascular smooth muscle cells, and/or perivascular adipocytes), independently of changes in the metabolic profile (e.g. glucose tolerance and/or plasma lipoprotein levels), leading to improved endothelium-derived nitric oxide-mediated vasodilatation and attenuated endothelium-derived cyclooxygenase-dependent vasoconstriction...Therefore, AMPK activation is not necessarily beneficial in terms of endothelial function. The contribution of endothelial AMPK in the regulation of vascular tone, in particular in the microvasculature where EDH plays a more important role, remains to be characterized."

Journal • Review