pf-04971729 and glimepiride

Combining antihyperglycemic agents in order to rapidly and safely achieve the best possible glycemic control is the standard of care today for the management of type 2 diabetes. Agents should ideally have mechanisms of actions that are complementary and that improve glycemic control without unacceptable gain in body weight or hypoglycemia. Areas covered: Ertugliflozin and metformin hydrochloride (ertugliflozin/metformin, SEGLUROMET) is a recently approved fixed-dose combination tablet containing the sodium-glucose co-transporter 2 (SGLT-2) inhibitor ertugliflozin and metformin. This review summarizes key characteristics of ertugliflozin and metformin, as well as the efficacy and safety results of co-administration of these agents in the ertugliflozin clinical development program. This information comes from the ertugliflozin/metformin prescribing information as well as published clinical trials obtained through a PubMed search. Expert commentary: SGLT-2 inhibitors are an important class of antihyperglycemic agents that are efficacious as monotherapy and in combination with other antihyperglycemic agents. Given their favorable effects on glycemia control as well as 'extra-glycemic' parameters such as body weight and blood pressure, they are ideal agents for appropriate patients with type 2 diabetes. The fixed-dose combination of ertugliflozin with metformin is an effective combination that is conveniently administered and may improve medication adherence and persistence.

Topics: Bridged Bicyclo Compounds, Heterocyclic; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Combinations; Humans; Hypoglycemic Agents; Metformin; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Sulfonylurea Compounds; Treatment Outcome

Ertugliflozin, a sodium-glucose cotransporter 2 inhibitor for the treatment of adults with type 2 diabetes mellitus, is expected to be coadministered with sitagliptin, metformin, glimepiride, and/or simvastatin. Four separate open-label, randomized, single-dose, crossover studies were conducted in healthy adults to assess the potential pharmacokinetic interactions between ertugliflozin 15 mg and sitagliptin 100 mg (n = 12), metformin 1000 mg (n = 18), glimepiride 1 mg (n = 18), or simvastatin 40 mg (n = 18). Noncompartmental pharmacokinetic parameters derived from plasma concentration-time data were analyzed using mixed-effects models to assess interactions. Coadministration of sitagliptin, metformin, glimepiride, or simvastatin with ertugliflozin had no effect on area under the plasma concentration-time profile from time 0 to infinity (AUC

Topics: Adolescent; Adult; Bridged Bicyclo Compounds, Heterocyclic; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Interactions; Drug Therapy, Combination; Female; Glucuronosyltransferase; Healthy Volunteers; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Sitagliptin Phosphate; Sulfonylurea Compounds; UDP-Glucuronosyltransferase 1A9; Young Adult

To evaluate the long-term efficacy and safety of ertugliflozin in adults with type 2 diabetes mellitus inadequately controlled on metformin.. A 104-week Phase III, randomized double-blind study with a 26-week placebo-controlled period (Phase A) and a 78-week period (Phase B) where blinded glimepiride was added to non-rescued placebo participants with fasting fingerstick glucose ≥6.1 mmol/L. Results through week 104 are reported.. Mean (standard error) change in HbA1c from baseline was -0.7% (0.07) and -1.0% (0.07) at week 52; -0.6% (0.08) and -0.9% (0.08) at week 104 for ertugliflozin 5 and 15 mg. At week 52, 34.8% and 36.6% participants had HbA1c <7.0%, and 24.6% and 33.7% at week 104, for ertugliflozin 5 and 15 mg. Ertugliflozin reduced fasting plasma glucose (FPG), body weight and systolic blood pressure (SBP) from baseline through week 104. The incidence of female genital mycotic infections (GMIs) was higher with ertugliflozin, and symptomatic hypoglycaemia was lower for ertugliflozin versus placebo/glimepiride. Minimal bone mineral density (BMD) changes were observed, similar to placebo/glimepiride, except at total hip where reduction in BMD was greater with ertugliflozin 15 mg versus placebo/glimepiride: difference in least squares means (95% CI) -0.50% (-0.95, -0.04) at week 52 and -0.84% (-1.44, -0.24) at week 104.. Ertugliflozin maintained improvements from baseline in HbA1c, FPG, body weight and SBP through week 104. Ertugliflozin was well tolerated, with non-clinically relevant changes in BMD. Compared with placebo/glimepiride, ertugliflozin increased female GMIs, but reduced the incidence of symptomatic hypoglycaemia. ClinicalTrials.gov Identifier: NCT02033889.

Topics: Aged; Blood Glucose; Bone Density; Bridged Bicyclo Compounds, Heterocyclic; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Mycoses; Reproductive Tract Infections; Sulfonylurea Compounds; Vulvovaginitis