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Effects of MK-0941, a novel glucokinase activator, on glycemic control in insulin-treated patients with type 2 diabetes.

ABSTRACT: 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. before meals (a.c.). This study included an initial 14-week, dose-ranging phase followed by a 40-week treatment phase during which patients were to be uptitrated as tolerated to 40 mg (or placebo) t.i.d. a.c. The primary efficacy end point was change from baseline in A1C at Week 14.At Week 14, A1C and 2-h postmeal glucose (PMG) improved significantly versus placebo with all MK-0941 doses. Maximal placebo-adjusted least squares mean changes from baseline in A1C (baseline A1C 9.0%) and 2-h PMG were -0.8% and -37 mg/dL (-2 mmol/L), respectively. No significant effects on fasting plasma glucose were observed at any dose versus placebo. By 30 weeks, the initial glycemic responses noted at 14 weeks were not sustained. MK-0941 at one or more doses was associated with significant increases in the incidence of hypoglycemia, triglycerides, systolic blood pressure, and proportion of patients meeting criteria for predefined limits of change for increased diastolic blood pressure.In patients receiving stable-dose insulin glargine, the GKA MK-0941 led to improvements in glycemic control that were not sustained. MK-0941 was associated with an increased incidence of hypoglycemia and elevations in triglycerides and blood pressure.

SUBMITTER: Meininger GE

PROVIDER: S-EPMC3220852 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Effects of MK-0941, a novel glucokinase activator, on glycemic control in insulin-treated patients with type 2 diabetes.

Meininger Gary E GE Scott Russell R Alba Maria M Shentu Yue Y Luo Edmund E Amin Himal H Davies Michael J MJ Kaufman Keith D KD Goldstein Barry J BJ

Diabetes care 20111012 12

<h4>Objective</h4>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.<h4>Research design and methods</h4>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. before meals (a.c.). This study included an initial 14-week, dose-ranging phase followed by a 40-week ...[more]

PMID: 21994424

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Project description:Importance:Numerous factors are associated with the ability of patients with type 2 diabetes to achieve optimal glycemic control. However, many of these factors are not modifiable by quality improvement interventions. In contrast, the structure of how diabetes care is delivered, such as whether patients visit an endocrinologist or how prescriptions are filled, is potentially modifiable, yet its associations with glycemic control have not been rigorously evaluated. Objective:To investigate the association of diabetes care delivery with glycemic control in patients with type 2 diabetes using insulin. Design, Setting, and Participants:This retrospective cohort study used baseline claims and laboratory insurer data within a large pragmatic trial to identify individuals with type 2 diabetes using insulin with data for at least 1 hemoglobin A1c (HbA1c) test result from before trial randomization (July 1, 2014, to October 5, 2016) and for key nonmodifiable patient factors as well as diabetes care delivery and behavioral factors measured before the HbA1c test. Analyses were conducted from February 4, 2017, to November 13, 2018. Main Outcomes and Measures:Multivariable modified Poisson regression was used to evaluate the independent associations of nonmodifiable patient factors and potentially modifiable diabetes care delivery and patient behavioral factors with achieving adequate diabetes control (ie, HbA1c level <8%). The extent of measured variation explained in glycemic control by these factors was also explored using pseudo R2 and C statistics. Results:Of 1423 patients included, 565 (39.7%) were women, and the mean (SD) age was 56.4 (9.0) years. In total, 690 (48.5%) had HbA1c levels less than 8%. Age (relative risk [RR] per 1-unit increase, 1.01; 95% CI, 1.00-1.02), persistent use of basal insulin (RR, 1.20; 95% CI, 1.00-1.43), more frequent filling of glucose self-testing supplies (RR, 1.01; 95% CI, 1.01-1.02), visiting an endocrinologist (RR, 1.41; 95% CI, 1.19-1.67), and receipt of insulin prescriptions by mail order (RR, 1.23; 95% CI, 1.03-1.48) were all independently associated with adequate control. Measured potentially modifiable diabetes care factors explained more variation in adequate glycemic control than measured nonmodifiable patient factors (C statistic, 0.661 vs 0.598; pseudo R2 = 0.11 vs 0.04). Conclusions and Relevance:These findings suggest that for patients with type 2 diabetes using insulin, the way in which care is delivered may be more strongly associated with achieving adequate control of HbA1c levels than patient factors that cannot be altered are. Given the potential for intervention, these care delivery factors could be the focus of efforts to improve diabetes outcomes.

Project description:ImportanceContinuous glucose monitoring (CGM) has been shown to be beneficial for adults with type 2 diabetes using intensive insulin therapy, but its use in type 2 diabetes treated with basal insulin without prandial insulin has not been well studied.ObjectiveTo determine the effectiveness of CGM in adults with type 2 diabetes treated with basal insulin without prandial insulin in primary care practices.Design, setting, and participantsThis randomized clinical trial was conducted at 15 centers in the US (enrollment from July 30, 2018, to October 30, 2019; follow-up completed July 7, 2020) and included adults with type 2 diabetes receiving their diabetes care from a primary care clinician and treated with 1 or 2 daily injections of long- or intermediate-acting basal insulin without prandial insulin, with or without noninsulin glucose-lowering medications.InterventionsRandom assignment 2:1 to CGM (n = 116) or traditional blood glucose meter (BGM) monitoring (n = 59).Main outcomes and measuresThe primary outcome was hemoglobin A1c (HbA1c) level at 8 months. Key secondary outcomes were CGM-measured time in target glucose range of 70 to 180 mg/dL, time with glucose level at greater than 250 mg/dL, and mean glucose level at 8 months.ResultsAmong 175 randomized participants (mean [SD] age, 57 [9] years; 88 women [50%]; 92 racial/ethnic minority individuals [53%]; mean [SD] baseline HbA1c level, 9.1% [0.9%]), 165 (94%) completed the trial. Mean HbA1c level decreased from 9.1% at baseline to 8.0% at 8 months in the CGM group and from 9.0% to 8.4% in the BGM group (adjusted difference, -0.4% [95% CI, -0.8% to -0.1%]; P = .02). In the CGM group, compared with the BGM group, the mean percentage of CGM-measured time in the target glucose range of 70 to 180 mg/dL was 59% vs 43% (adjusted difference, 15% [95% CI, 8% to 23%]; P < .001), the mean percentage of time at greater than 250 mg/dL was 11% vs 27% (adjusted difference, -16% [95% CI, -21% to -11%]; P < .001), and the means of the mean glucose values were 179 mg/dL vs 206 mg/dL (adjusted difference, -26 mg/dL [95% CI, -41 to -12]; P < .001). Severe hypoglycemic events occurred in 1 participant (1%) in the CGM group and in 1 (2%) in the BGM group.Conclusions and relevanceAmong adults with poorly controlled type 2 diabetes treated with basal insulin without prandial insulin, continuous glucose monitoring, as compared with blood glucose meter monitoring, resulted in significantly lower HbA1c levels at 8 months.Trial registrationClinicalTrials.gov Identifier: NCT03566693.

Project description:BACKGROUND:Blood glucose control is closely related to type 2 diabetes mellitus (T2DM) prognosis. This multicenter study aimed to investigate blood glucose control among patients with insulin-treated T2DM in North China and explore the application value of combining an elastic network (EN) with a machine-learning algorithm to predict glycemic control. METHODS:Basic information, biochemical indices, and diabetes-related data were collected via questionnaire from 2787 consecutive participants recruited from 27 centers in six cities between January 2016 and December 2017. An EN regression was used to address variable collinearity. Then, three common machine learning algorithms (random forest [RF], support vector machine [SVM], and back propagation artificial neural network [BP-ANN]) were used to simulate and predict blood glucose status. Additionally, a stepwise logistic regression was performed to compare the machine learning models. RESULTS:The well-controlled blood glucose rate was 45.82% in North China. The multivariable analysis found that hypertension history, atherosclerotic cardiovascular disease history, exercise, and total cholesterol were protective factors in glycosylated hemoglobin (HbA1c) control, while central adiposity, family history, T2DM duration, complications, insulin dose, blood pressure, and hypertension were risk factors for elevated HbA1c. Before the dimensional reduction in the EN, the areas under the curve of RF, SVM, and BP were 0.73, 0.61, and 0.70, respectively, while these figures increased to 0.75, 0.72, and 0.72, respectively, after dimensional reduction. Moreover, the EN and machine learning models had higher sensitivity and accuracy than the logistic regression models (the sensitivity and accuracy of logistic were 0.52 and 0.56; RF: 0.79, 0.70; SVM: 0.84, 0.73; BP-ANN: 0.78, 0.73, respectively). CONCLUSIONS:More than half of T2DM patients in North China had poor glycemic control and were at a higher risk of developing diabetic complications. The EN and machine learning algorithms are alternative choices, in addition to the traditional logistic model, for building predictive models of blood glucose control in patients with T2DM.

Dataset Information

Effects of MK-0941, a novel glucokinase activator, on glycemic control in insulin-treated patients with type 2 diabetes.

Publications

Effects of MK-0941, a novel glucokinase activator, on glycemic control in insulin-treated patients with type 2 diabetes.

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