Keith D Kaufman

Merck & Co. | MSD · Clinical Research

Background and aims: This study assessed the effects of the GLP-1/glucagon receptor co-agonist efinopegdutide relative to the selective GLP-1 receptor agonist semaglutide on liver fat content (LFC) in patients with nonalcoholic fatty liver disease (NAFLD). Methods: This was a Phase 2a, randomized, active-comparator-controlled, parallel-group, op...

Background We examined the efficacy and safety of corifollitropin alfa (CFA) combined with human chorionic gonadotropin (hCG) for the induction of testicular growth and pubertal development in adolescent boys with hypogonadotropic hypogonadism (HH). Methods This was a 64-week, multi-center, open-label, single-group study of CFA in adolescent males...

Objective To assess the efficacy and safety of DPP-4 inhibition with sitagliptin in youth with type 2 diabetes (T2D). Study Design This was a 54-week, double-blind, randomized, controlled clinical trial evaluating the safety and efficacy of DPP-4 inhibition with sitagliptin 100 mg once daily as initial oral therapy in youth with T2D. The 190 parti...

Objective To assess the efficacy and safety of sitagliptin in youth with type 2 diabetes (T2D) inadequately controlled with metformin ± insulin. Study Design Data were pooled from two 54-week, double-blind, randomized, placebo-controlled studies of sitagliptin 100 mg daily or placebo added onto treatment of 10- to 17-year-old youth with T2D and in...

Objective: Phenotypic heterogeneity among patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) is ill defined. We used cluster analysis machine-learning algorithms to identify phenotypes among trial participants with T2DM and ASCVD. Research design and methods: We used data from the Trial Evaluating Ca...

Aims: To assess the efficacy, safety, and tolerability of ipragliflozin 50 mg once daily (q.d.) added to sitagliptin 50 mg q.d. monotherapy in Japanese patients with type 2 diabetes (T2D). Materials and methods: The results of two clinical trials are reported. In both, patients had HbA1c 7.0-10.0% on sitagliptin 50 mg q.d. 2 weeks prior to addit...

Aims: To investigate the efficacy, safety and tolerability of sitagliptin 50 mg once daily (q.d.) added to ipragliflozin 50 mg q.d. monotherapy in Japanese patients with type 2 diabetes (T2D). Materials and methods: Japanese patients with T2D and HbA1c 7.0-10.0% while treated with ipragliflozin 50 mg q.d. were randomized 1:1 to additional treatm...

IntroductionOlder patients with type 2 diabetes (T2D) are at increased risk of diabetic nephropathy and mild renal insufficiency. This analysis compared the anti-hyperglycemic efficacy and safety of sitagliptin with dapagliflozin in patients ≥ 65 years of age with T2D and mild renal insufficiency.Methods This was a post hoc analysis of data from 41...

BACKGROUND Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis....

Background: Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis...

Approved antihyperglycemic therapies for pediatric patients with T2D are currently limited to metformin (MET) and insulin. SITA is being evaluated in 3 studies in patients 10-17 years of age with T2D: SITA as initial oral therapy, MK-0431 P083; SITA as add-on to MET administered as a fixed dose combination (FDC), MK-0431A P170; and SITA as add-on t...

MK-0431-P083, a multinational, 54-week, phase III study of the DPP-4 inhibitor sitagliptin (SITA) as initial oral therapy in patients 10-17 years of age with T2D, was initiated in 2012 and completed enrollment in 2018. A total of 201 patients with T2D who were either drug-naïve or on insulin alone at study entry were randomized and treated. Baselin...

In the U.S., ~45% of patients with T2D are ≥65 years old, of whom ~50% have mild renal insufficiency (eGFR ≥60 and <90 mL/min/1.73 m2). Older people may respond to AHA treatment differently from younger people, and assessments focused on the older population are desirable. We conducted a post hoc analysis of the cohort of patients ≥65 years who par...

MK-0431-P083, a 54-week phase III study of the DPP-4 inhibitor sitagliptin as initial oral therapy in patients 10-17 years of age with T2D was initiated in 2012 and completed enrollment in 2018. After informed consent was obtained, patient screening was initiated with a screening visit (V1), followed by a single-blind, placebo run-in (V2) for 1 wee...

MET is generally recommended as the initial AHA for T2D, but many patients do not achieve glycemic goal at an initial, sub-maximal dose (500-1000 mg/day) and should intensify therapy. Typically, MET dose is first maximized, followed by addition of a second AHA as needed. This sequential approach can result in prolonged exposure to hyperglycemia. Th...

Aims To characterize the glycemic efficacy and safety of initiation of the DPP‐4 inhibitor sitagliptin during metformin dose escalation in participants with type 2 diabetes (T2D) not at HbA1c goal on a sub‐maximal dose of metformin. Materials and Methods Study participants with HbA1c ≥7.5% and ≤11.0% while on 1000 mg/day metformin were randomized...

Appendix S1. Supplementary Text. Figure S1. Mean systolic blood pressure (A) and body weight (B) through Week 24; black circles = sitagliptin, open circles = dapagliflozin. Table S1. List of participating investigators Table S2. Patient disposition; *one patient in the dapagliflozin group, associated with a protocol violation, was randomized but...

Aims: To compare the effects of continuing vs. discontinuing sitagliptin when initiating and intensively titrating insulin glargine. Materials and methods: Eligible patients had inadequately controlled type 2 diabetes on metformin (≥1500 mg/day) in combination with a dipeptidyl peptidase-4 inhibitor (DPP-4i) and/or a sulfonylurea. Those on metfo...

Aims To compare the efficacy and safety of the DPP‐4 inhibitor sitagliptin with the SGLT‐2 inhibitor dapagliflozin in patients with type 2 diabetes and mild renal insufficiency. Materials and Methods Patients with HbA1c 7.0 to 9.5% (53 to ≤80 mmol/mol) and eGFR 60 to <90 mL/min/1.73m² on metformin (≥1500 mg/day) ± sulfonylurea were randomized to s...

While choice of AHAs may be modified in patients with T2D and moderate or severe renal insufficiency, this is generally not the case in patients with mild renal insufficiency. Clinical trial data focused on this population, which represents ∼40% of patients with T2D, are lacking. In a randomized, double-blind, active comparator-controlled clinical...

DPP-4 inhibitors (DPP-4is) are often discontinued with initiation of insulin therapy but the impact of this discontinuation on efficacy and hypoglycemia has not been studied. In this double-blind trial the safety and efficacy of initiating insulin while continuing sitagliptin (SITA) was evaluated. Eligible patients had inadequately controlled T2DM...

Aims TECOS, a cardiovascular safety trial of 14,671 patients with type 2 diabetes and cardiovascular disease, demonstrated sitagliptin was non‐inferior to placebo for the primary composite cardiovascular outcome when added to best usual care. This study tested hypotheses that medical resource use and costs differed between these two treatment strat...

Abstract Background Type 2 diabetes (T2D) is a progressive disease that often requires a patient to use multiple antihyperglycemic agents to achieve glycemic control with disease progression. Omarigliptin is a once-weekly dipeptidyl peptidase-4 inhibitor. The purpose of this trial was to assess the efficacy and safety of adding omarigliptin to the...

Table S1. The least squares (LS) means (LDA model analysis) and arithmetic means of the changes from baseline in efficacy endpoints at Week 52. Table S2. Adverse events (AEs) summary; incidences of specific AEs by MedDRA SOC ‡, with incidence ≥5% in ≥1 treatment group; and incidences of symptomatic hypoglycemia at Week 52 (double‐blind + open‐labe...

Objective: We evaluated the specific causes of death and their associated risk factors in a contemporary cohort of patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD). Research design and methods: We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n = 14,671), a cardiovascu...

Aims: To assess the efficacy and safety of once-weekly omarigliptin as monotherapy in people with type 2 diabetes mellitus (T2DM). Methods: People with T2DM not on glucose-lowering medications, or who were washed-off monotherapy or low-dose dual therapy, were randomized double-blind to omarigliptin 25 mg (n=165) or matching omarigliptin placebo...

Background Omarigliptin is a once-weekly (q.w.) oral DPP-4 inhibitor that is approved for the treatment of patients with type 2 diabetes mellitus (T2DM) in Japan. To support approval of omarigliptin in the United States, the clinical development program included a cardiovascular (CV) safety study. Subsequently, a business decision was made not to s...

Purpose: The objective of this clinical trial was to assess the efficacy and safety of omarigliptin monotherapy in young adult patients with type 2 diabetes mellitus (T2DM). Unexpected efficacy results in this trial led to a series of investigations that identified the use of prohibited medication by a substantial number of trial patients. Method...

Objective: To examine the efficacy and safety of the once-weekly (q.w.) dipeptidyl peptidase-4 inhibitor, omarigliptin, in patients with type 2 diabetes (T2DM) and inadequate glycemic control on metformin monotherapy. Methods: In a randomized, double-blind trial, patients with T2DM on a stable dose of metformin monotherapy (≥1500 mg/day) with gl...

Objective: To evaluate the efficacy and safety of adding the once-weekly DPP-4 inhibitor omarigliptin or the sulfonylurea glimepiride to the treatment regimen of patients with type 2 diabetes (T2DM) and inadequate glycemic control on metformin monotherapy. Methods: Patients with T2DM and HbA1c ≥6.5% to ≤9.0% while on a stable dose of metformin (...

Aims: To assess the safety and efficacy of omarigliptin in Japanese patients with type 2 diabetes (T2D). Materials and methods: In a 24-week double-blind trial, 414 patients with T2D were randomized to omarigliptin 25 mg once-weekly (q.w.), sitagliptin 50 mg once daily (q.d.) or placebo. The double-blind period was followed by a 28-week open-lab...

Table S1. Incidence of subjects with amylase or lipase values > upper limit of normal (ULN), >1.5 ULN or >3X ULN. Figure S1. Study design; T2DM = type 2 diabetes mellitus; q.w. = once weekly; q.d. = once daily; R = randomization. Figure S2. Disposition of subjects. Figure S3. Percentage of subjects at HbA1c goals of <7.0% or <6.5% at Week 24. Pe...

Aim: To compare the efficacy and safety of the once-weekly oral dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin or once-daily DPP-4 inhibitor sitagliptin in patients with type 2 diabetes (T2DM) and inadequate glycaemic control on metformin. Materials and methods: Patients with T2DM with a glycated haemoglobin (HbA1c) concentration ≥6.5% to...

Objective: Limited data exist regarding safety and efficacy of antihyperglycemic drugs in older patients with type 2 diabetes. The Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) was a randomized, double-blind, placebo-controlled trial assessing the impact of sitagliptin on a primary composite outcome of cardiovascular death, non...

Objective: To evaluate the safety and efficacy of sitagliptin when added to the treatment of patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on acarbose monotherapy. Research design and methods: This was a multicenter, randomized, placebo-controlled, double-blind clinical trial. Patients (N = 381) with T2DM and inadequ...

Objective: Type 2 diabetes is associated with increased fracture risk, further elevated by treatments such as thiazolidinediones and sodium-glucose co-transporter-2 inhibitors. As data regarding dipeptidyl peptidase-4 inhibitors are mixed, we examined fracture incidence in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Res...

Table S1 | Patient disposition Figure S1 | Change from baseline in glycated hemoglobin (%) by week.

Aims/introduction: To assess the efficacy and safety of initial combination therapy with sitagliptin and metformin in Chinese patients with type 2 diabetes (T2DM) and inadequate glycemic control. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel group 24-week clinical trial conducted in China. Patients (N=74...

Background: Type 2 diabetes (T2DM) treatment generally requires multiple antihyperglycemic agents. When diet, exercise and treatment with sulfonylurea and metformin do not achieve glycemic goals, several options are available. This study evaluated the efficacy and tolerability of sitagliptin 100 mg/day added to therapy with sulfonylurea and metfor...

This study was conducted to determine the optimal dose of omarigliptin, a once-weekly (q.w.) dipeptidyl peptidase IV (DPP-4) inhibitor, for the treatment of patients with type 2 diabetes and evaluate the long-term safety of that dose. In a multicenter, double-blind, 12-week, dose-range finding study, 685 oral antihyperglycemic agent-naïve or washed...

Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-labe...

Background: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. Methods: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing the...

Objective: To evaluate the efficacy of once daily sitagliptin 100 mg as monotherapy or as add-on to metformin in patients with type 2 diabetes mellitus (T2DM) over 2 years of treatment. Research design and methods: The monotherapy analysis used pooled 104 week data from 64 patients in two randomized, double-blind trials evaluating the safety and...

The objective of this study was to assess the effect of sitagliptin on insulin dose in patients with inadequately controlled type 2 diabetes who titrate basal insulin to a target fasting glucose level after initiating sitagliptin. This was a multicenter, randomized, double-blind, placebo-controlled, 24-week clinical trial in which treatment with si...

In the USA, 45% of patients with type 2 diabetes mellitus (T2DM) are elderly (≥ 65 years old). In general, use of sulfonylurea increases with patient age as does the associated risk for hypoglycaemia, and the consequences of hypoglycaemia can be more pronounced in elderly patients. Sitagliptin, a DPP-4 inhibitor, improves glycaemic control in adult...

Impaired renal function is a major complication of type 2 diabetes mellitus (T2DM). Mild renal impairment is present in 38% of patients with T2DM and may impact choice of antihyperglycemic agent. Sulfonylureas and dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used to treat hyperglycemia in patients with T2DM and renal impairment. Although...

The aim of this study was to evaluate the safety and tolerability of sitagliptin 100 mg/day in elderly patients with type 2 diabetes. A post hoc pooled analysis of 25 randomized, double-blind, parallel group clinical studies with results available as of 1 December 2011. Multicenter, international clinical trials. Patients with type 2 diabetes aged...

Sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, lowers blood glucose when administered as monotherapy or in combination with other antihyperglycemic agents. TECOS will evaluate the effects of adding sitagliptin to usual diabetes care on cardiovascular outcomes and clinical safety. TECOS is a pragmatic, academically run, multinational, random...

To evaluate the efficacy and safety of initial combination therapy of sitagliptin 100 mg/day coadministered with all marketed doses of pioglitazone in patients with type 2 diabetes. Patients with A1C ≥7.5% and ≤11.0% were randomized among 7 arms that received, once daily, 100 mg sitagliptin alone, 15, 30, or 45 mg pioglitazone alone, or 100 mg sita...

Aims: The effects of sitagliptin and pioglitazone, alone and in combination, on α- and β-cell function were assessed in patients with type 2 diabetes. Methods: Following a 6-week diet/exercise period, 211 patients with HbA1c of 6.5-9.0% and fasting plasma glucose of 7.2-14.4 mmol/l were randomized (1 :1 :1 : 1) to sitagliptin, pioglitazone, sita...

Objective: The American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) diabetes algorithm recommends a stratified approach to initial therapy to achieve a glycated hemoglobin (HbA1c) goal of ≤6.5% in patients with type 2 diabetes mellitus (T2DM) who have inadequate glycemic control. Data from a double-bli...

Introduction In a previous pooled analysis of 19 double-blind clinical studies conducted by Merck, which included data available as of July 2009 on 10,246 patients with type 2 diabetes (T2DM), treatment with sitagliptin was shown to be generally well tolerated compared with treatment with control agents. As the sitagliptin clinical development prog...

Background: Treatment with oral antihyperglycemic agents has not been well characterized in patients with type 2 diabetes and end-stage renal disease (ESRD). The efficacy and safety of sitagliptin and glipizide monotherapy in patients with type 2 diabetes and ESRD on dialysis therapy were assessed in this study. Study design: 54-week, randomized...

Objective To compare the incidence of cardiovascular events and mortality in patients with type 2 diabetes mellitus treated with sitagliptin or non-sitagliptin comparators. Methods A post hoc assessment of cardiovascular safety in 14,611 patients was performed by pooling data from 25 double-blind studies, which randomised patients at baseline to s...

OBJECTIVE Patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease have an increased risk of micro- and macrovascular disease, but limited options for antihyperglycemic therapy. We compared the efficacy and safety of sitagliptin with glipizide in patients with T2DM and moderate-to-severe chronic renal insufficiency and inadequate gl...

Aims: To assess efficacy and safety of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in combination therapy with metformin (≥1500 mg/day) and pioglitazone (≥30 mg/day) in patients with type 2 diabetes (T2DM) with inadequate glycemic control (hemoglobin A1c [HbA1c] ≥7.5% and ≤11%). Methods: This placebo-controlled, double-blind study included...

Background: New therapeutic approaches are needed to improve glycemic control in patients with type 2 diabetes (T2D), a progressive disorder that often requires combination therapy. The present study assessed the efficacy and safety of sitagliptin as add-on therapy to metformin and rosiglitazone in patients with T2D. Methods: The present study w...

In a previously-published study, adding sitagliptin or glipizide to ongoing metformin therapy provided similar HbA(1c) improvement (both groups, -0.7%) after 52 weeks in patients with type 2 diabetes (T2DM). Significantly fewer patients experienced symptomatic hypoglycemia with sitagliptin (5% of 588 patients) compared to glipizide (32% of 584 pati...

  The present study was conducted to evaluate the efficacy, safety and tolerability of sitagliptin added to ongoing metformin therapy in Chinese patients with type 2 diabetes (T2DM) who failed to achieve adequate glycemic control with metformin monotherapy.   After a metformin titration/stabilization period and a 2-week, single-blind, placebo run-i...

To assess the 54-week efficacy of initial combination therapy with sitagliptin and pioglitazone, compared with pioglitazone monotherapy, and to assess safety in these groups during the 30 weeks after the dosage of pioglitazone was increased from 30 to 45 mg/day, in drug-naÏve patients with type 2 diabetes mellitus and inadequate glycaemic control [...

Finasteride (1 mg) has been shown to increase vertex hair growth in men aged 18 to 60 years with male pattern hair loss and to increase frontal scalp hair growth in subjects aged 18 to 41 years. A secondary efficacy analysis was conducted to determine effects of finasteride (1 mg) on scalp hair growth in the 4 distinct scalp regions affected by mal...

To assess the efficacy and safety of MK-0941, a glucokinase activator (GKA), when added to stable-dose insulin glargine in patients with type 2 diabetes. In this double-blind study, 587 patients taking stable-dose insulin glargine (±metformin ≥1,500 mg/day) were randomized (1:1:1:1:1) to MK-0941 10, 20, 30, or 40 mg or matching placebo t.i.d. befor...

To evaluate the efficacy and safety of initial therapy with a fixed-dose combination (FDC) of sitagliptin and metformin compared with pioglitazone in drug-naÏve patients with type 2 diabetes. After a 2-week single-blind placebo run-in period, patients with type 2 diabetes, HbA1c of 7.5-12% and not on antihyperglycaemic agent therapy were randomized...

The efficacy and safety of sitagliptin (SITA) monotherapy and SITA/metformin (MET) vs. pioglitazone (PIO) were assessed in patients with type 2 diabetes and moderate-to-severe hyperglycaemia (A1C = 7.5-12.0%). In an initial 12-week phase (Phase A), 492 patients were randomised 1 : 1 in a double-blind fashion to SITA (100 mg qd) or PIO (15 mg qd, up...

To examine the effect of sitagliptin and metformin, alone and in combination, on modelled parameters of β-cell function in patients with type 2 diabetes. The data used in the present analyses are from a 104-week study, which included a 24-week, placebo- and active controlled phase followed by a 30-week, active controlled, continuation phase and an...

We examined the effects of the 11β-hydroxysteroid dehydrogenase type 1 (HSD1) inhibitor, MK-0916, on the multiple components of the metabolic syndrome (MetS) in patients with type 2 diabetes (T2DM) and MetS. This was a 12-week, multicentre, randomized, double-blind, placebo-controlled study. Patients with T2DM (mean baseline A1C: 7.3%) and National...

Combination therapy with sitagliptin and metformin has shown superior efficacy compared with metformin monotherapy. In this study, we compare two strategies: initial combination therapy with sitagliptin/metformin as a fixed-dose combination (FDC) and initial metformin monotherapy, with the option to add additional antihyperglycaemic agents (AHAs) i...

Sitagliptin and glipizide added to metformin provided similar degrees of glycemic efficacy in patients with type 2 diabetes with inadequate glycemic control on metformin monotherapy at 1 year; however, significantly more patients in the sitagliptin group achieved an A1C reduction of >0.5% without hypoglycemia and without an increase in body weight.

This study was conducted to compare the glycaemic efficacy and safety of initial combination therapy with the fixed-dose combination of sitagliptin and metformin versus metformin monotherapy in drug-naive patients with type 2 diabetes. This double-blind study (18-week Phase A and 26-week Phase B) randomized 1250 drug-naÏve patients with type 2 diab...

Type 2 diabetes in the elderly is an important and insufficiently studied public health problem. This study evaluated sitagliptin monotherapy in patients with type 2 diabetes aged ≥ 65 years. This was a randomized, double-blind, placebo-controlled, parallel-group study conducted at 52 sites in the United States. Patients were treated with once-dail...

to evaluate the efficacy and safety of adding sitagliptin or glimepiride to the treatment regimen of patients with type 2 diabetes mellitus and inadequate glycaemic control on metformin monotherapy. patients with type 2 diabetes and an HbA(1c) of 6.5-9.0% while on a stable dose of metformin (≥ 1500 mg/day) combined with diet and exercise for at lea...

To assess the safety and efficacy of initial combination therapy with sitagliptin and pioglitazone compared with pioglitazone monotherapy in drug-naïve patients with type 2 diabetes. A total of 520 patients were randomised to initial combination therapy with sitagliptin 100 mg q.d. and pioglitazone 30 mg q.d. or pioglitazone 30 mg q.d. monotherapy...

To evaluate the efficacy and safety of taranabant in overweight and obese patients with type 2 diabetes mellitus (T2DM). This was a multicenter, double-blind, randomized, placebo-controlled study in overweight and obese patients with T2DM (ages > or = 18 and < or = 75 years) with a BMI > or = 27 kg/m(2) and < or = 43 kg/m(2) and HbA1c > or =7.0 and...