Least Squares Mean Change In HbA1c Research Articles

55-OR: HSK7653, a Novel Ultralong-Acting DPP-4 Inhibitor, as Monotherapy in Patients With Type 2 Diabetes—A Randomized, Double-Blind, Placebo-Controlled Phase III Trial

Background: HSK7653 is a novel ultralong-acting DPP-4 inhibitor that maintains the average plasma DPP-4 inhibition over 80% for 14 days after 10mg or 25mg dosing. This randomized, double-blind, placebo-controlled phase III trial was conducted to evaluate the efficacy and safety of HSK7653 biweekly as monotherapy for 52 weeks in drug naive type 2 diabetes patients with inadequate glycemic control on diet and exercise. Methods: A total of 475 patients with a mean HbA1c level of 8.1% were randomized to HSK7653 10mg, 25mg or placebo biweekly at a ratio of 1:1:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label extension treatment with HSK7653 25mg for all patients. The primary endpoint was the change in HbA1c from baseline at 24 weeks. Results: At week 24, the least-squares mean change in HbA1c from baseline was -0.96% in HSK7653 10mg, -0.92% in HSK7653 25mg and -0.33% in placebo. HSK7653 10mg and 25mg treatment resulted in significant placebo-subtracted changes in HbA1c of -0.63% (95% CI: -0.81%, -0.46%, p<0.0001) and -0.59% (95% CI: -0.77%, -0.42%, p<0.0001), respectively. The percentage of patients achieving HbA1c<7.0% was 44.2% in HSK7653 10mg group and 44.4% in HSK7653 25mg group versus 20.6% in placebo group (p<0.0001 for HSK7653 groups vs. placebo). No meaningful body weight changes were observed in all treatment groups. In the open-label extension treatment (from week 24 to week 52), the sustaining reduction of HbA1c from baseline were observed in HSK7653 10mg switched to 25mg group and HSK7653 25mg maintenance group. There were no excess hypoglycemia events in HSK7653 vs. placebo, and the incidence of adverse events was similar in all groups during the treatment. Conclusions: In people with type 2 diabetes who had inadequate glycemic control on diet and exercise, HSK7653 monotherapy significantly improved glycemic control with well tolerability and safety. Clinical trial information: NCT04556851. Disclosure L.Ji: Other Relationship; Eli Lilly and Company, Novo Nordisk, Merck & Co., Inc., Bayer Inc., Sanofi-Aventis U.S., Roche Pharmaceuticals, MSD Life Science Foundation, AstraZeneca, Boehringer Ingelheim Inc., Abbott, Metronics. F.Bian: None. T.Pan: None. H.Jiang: None. C.Jiang: None. Q.Ren: None.

Efficacy, safety and cost-effectiveness comparison between U-100 human regular insulin and rapid acting insulin when delivered by V-Go wearable insulin delivery device in type 2 diabetes

IntroductionWe compared the efficacy and safety of human regular insulin (HRI) versus rapid-acting insulin (RAI) in a type 2 diabetes population already using the V-Go insulin delivery device.Research design and...

A pragmatic study of mid-mixture insulin and basal insulin treatment in patients with type 2 diabetes uncontrolled with oral antihyperglycaemic medications: A lesson from real-world experience.

BackgroundChinese guidelines for the treatment of type 2 diabetes (T2D) recommend basal or premixed insulins as insulin starters after failed oral antihyperglycaemic medication (OAM). This pragmatic study compared effectiveness and safety of add‐on basal insulin analog (BI) and mid‐mixture insulin analog (MMI; 50:50 premixed insulin) as starter insulin regimens in Chinese patients with T2D in a real‐world setting.Materials and MethodsThis was a multicentre, open‐label, randomized, parallel, pragmatic trial. Patients receiving OAMs were randomized 1:1 to BI (n = 410) or MMI (n = 404) for 24 weeks. Insulin titration and OAM adjustment were determined by investigators following usual standard‐of‐care. The primary outcome was change in glycated haemoglobin (HbA1c) from baseline.ResultsLeast‐squares mean changes in HbA1c from baseline to week 24 were −2.00% and −2.15% for BI and MMI groups, respectively (P = .13). The MMI group demonstrated a greater reduction in concomitant OAM therapies used than BI group (53.8% vs. 35.3%, respectively; P < .001). Very limited daily insulin dose increments were observed from baseline to week 24 in both BI and MMI groups (2.5 U/day and 1.8 U/day, respectively). Although both insulin analogs were well‐tolerated without severe hypoglycaemia, small weight gains were seen with both treatments. Higher total hypoglycaemia rates were noticed with the MMI group, while nocturnal hypoglycaemia events were comparable.ConclusionsIn real‐world settings, BI and MMI provided similar improvement in glucose control without conceding hypoglycaemia. The BI group received a greater number of OAMs in real‐world settings. Limited insulin dose titration was observed, while more adjustments occurred with OAM usage.

Long-Term, Real-World Safety and Efficacy of Teneligliptin: A Post-Marketing Surveillance of More Than 10,000 Patients with Type2 Diabetes in Japan.

IntroductionTeneligliptin is a dipeptidyl peptidase 4 inhibitor that was approved for the treatment of type 2 diabetes mellitus (T2DM) in Japan in 2012. We performed a long-term post-marketing surveillance (RUBY) to obtain real-world evidence regarding the safety and efficacy of teneligliptin in Japan.MethodsThis 3-year follow-up RUBY surveillance registered patients with T2DM who started treatment with teneligliptin between May 2013 and February 2015 in Japan. Collected data included demographics, treatments, adverse drug reactions (ADRs) and laboratory variables. Data were evaluated in all patients and in patients divided according to baseline renal function across categories of estimated glomerular filtration rate (G1–G5) and dialysis. Safety was assessed as the incidence of ADRs and efficacy was assessed in terms of glycaemic control, for up to 3 years.ResultsOf 11,677 patients registered, 10,696 and 10,249 were evaluable for safety and efficacy analyses, respectively. The median duration of exposure was 1096 days. ADRs occurred in 412 patients (3.85%) and were serious in 117 patients (1.09%). The most frequent ADR class was gastrointestinal disorders (0.68%), which included constipation. There were no new ADRs warranting attention beyond those already described in teneligliptin’s package insert. ADRs and serious ADRs in renal function subgroups occurred in 3.24–7.14% and 0.65–5.36% in G1–G5, and 4.49% and 1.92% in patients on dialysis, respectively. Reduction in HbA1c was sustained for 3 years after starting teneligliptin (− 0.70% ± 1.36%, p < 0.001 at 3 years). The least-squares mean changes in HbA1c adjusted for baseline were − 0.76% to − 0.66% in G1–G5 at 3 years. Glycated albumin levels decreased in patients on dialysis (− 2.92% ± 4.78% at 3 years).ConclusionThere were no new safety or efficacy concerns about teneligliptin used in long-term, real-world, clinical settings in patients with T2DM with any stages of renal impairment.Trial registrationJapan Pharmaceutical Information Center clinical trials database identifier: Japic CTI-153047.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s12325-019-01189-w) contains supplementary material, which is available to authorized users.

Safety and Efficacy of Teneligliptin in Patients with Type 2 Diabetes Mellitus and Impaired Renal Function: Interim Report from Post-marketing Surveillance.

IntroductionTeneligliptin is a novel oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus (T2DM). Safety and efficacy of teneligliptin have been demonstrated in clinical studies; however, data supporting its use in patients with moderate or severe renal impairment are limited. This interim analysis of a post-marketing surveillance of teneligliptin, exploRing the long-term efficacy and safety included cardiovascUlar events in patients with type 2 diaBetes treated bY teneligliptin in the real-world (RUBY), aims to verify the long-term safety and efficacy of teneligliptin in Japanese patients with T2DM and impaired renal function.MethodsFor this analysis, we used the data from case report forms of the RUBY surveillance between May 2013 and June 2017. The patients were classified into G1–G5 stages of chronic kidney disease according to estimated glomerular filtration rate (eGFR) at initiation of teneligliptin treatment. Safety and efficacy were evaluated in these subgroups. Patients on dialysis were also assessed. Safety was assessed from adverse drug reactions (ADRs). Glycemic control was evaluated up to 2 years after teneligliptin initiation.ResultsA total of 11,677 patients were enrolled in the surveillance and 11,425 patient case-report forms were collected for the interim analysis. The incidence of ADRs in each subgroup was 2.98–6.98% of patients, with no differences in the ADR profile (including hypoglycemia and renal function ADRs) between subgroups. At 1 and 2 years after starting teneligliptin, the least-squares mean change in HbA1c adjusted to the baseline was − 0.68 to − 0.85% and − 0.71 to − 0.85% across the eGFR groups, respectively. Treatment with teneligliptin in patients on dialysis reduced or tended to reduce glycated albumin levels [− 2.29%, (p < 0.001) after 1 year; − 1.64%, (p = 0.064) after 2 years].ConclusionsDuring long-term treatment, teneligliptin was generally well tolerated in patients with any stage of renal impairment from normal to end-stage renal disease, including those on dialysis, and improved glycemic control.Trial Registration NumberJapic CTI-153047.FundingMitsubishi Tanabe Pharma Corporation and Daiichi Sankyo Co, Ltd.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0416-2) contains supplementary material, which is available to authorized users.

Efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes: a 54-week study

ABSTRACTObjective: To assess the 54-week efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes and inadequate glycemic control (HbA1c 7.5–11%) on diet and exercise.Methods and materials: This was multinational study conducted at 140 clinical sites in 18 countries. Following an initial 24-week, double-blind, placebo-controlled period, patients entered a double-blind continuation period for an additional 30 weeks. Following the week 24 evaluation, patients remained on their previously assigned active, oral treatments: sitagliptin 50 mg b.i.d. + metformin 1000 mg b.i.d. (S100 + M2000), sitagliptin 50 mg b.i.d. + metformin 500 mg b.i.d. (S100 + M1000), metformin 1000 mg b.i.d. (M2000), metformin 500 mg b.i.d. (M1000), and sitagliptin 100 mg q.d. (S100). Patients initially randomized to placebo were switched to M2000 (designated PBO/M2000) at week 24. This report summarizes the overall safety and tolerability data for the 54-week study and presents efficacy results for patients randomized to continuous treatments who entered the 30-week continuation period.Results: Of the 1091 randomized patients, 906 completed the 24-week placebo-controlled phase and 885 patients continued into the 30-week continuation period (S100 + M2000 n = 161, S100+M1000 n = 160, M2000 n = 153, M1000 n = 147, S100 n = 141, PBO/M2000 n = 123). At baseline, patients included in the efficacy analysis had mean age of 54 years, mean BMI of 32 kg/m2, mean HbA1c of 8.7% (8.5–8.8% across groups), and mean duration of type 2 diabetes of 4 years. At week 54, in the all-patients-treated analysis of continuing patients, least-squares (LS) mean changes in HbA1c from baseline were −1.8% (S100 + M2000), −1.4% (S100 + M1000), −1.3% (M2000), −1.0% (M1000), and −0.8% (S100). The proportions of continuing patients with an HbA1c < 7% at week 54 were 67% (S100 + M2000), 48% (S100 + M1000), 44% (M2000), 25% (M1000), and 23% (S100). For the patients completing treatment through week 54, LS mean changes in HbA1c from baseline were −1.9% (S100 + M2000), −1.7% (S100 + M1000), −1.6% (M2000), −1.2% (M1000), and −1.4% (S100). Glycemic response was generally durable over time across treatments. All treatments improved measures of β-cell function (e.g., HOMA-β, proinsulin/insulin ratio). Mean body weight decreased from baseline in the combination and metformin monotherapy groups and was unchanged from baseline in the sitagliptin monotherapy group. The incidence of hypoglycemia was low (1–3%) across treatment groups. The incidence of gastrointestinal adverse experiences with the co-administration of sitagliptin and metformin was similar to that observed with metformin alone.Limitations: The patient population evaluated in the 54-week efficacy analysis was a population of patients who entered the continuation period without receiving glycemic rescue therapy in the 24-week placebo-controlled period. Because the baseline HbA1c inclusion criteria ranged from 7.5 to 11% and the glycemic rescue criterion was an HbA1c > 8% after week 24, there was a greater likelihood of glycemic rescue in the monotherapy groups; this led to more missing data in the continuation all-patients-treated population(CAPT) analysis and fewer patients contributing to the completers analysis in the monotherapy groups.Conclusions: In this study, initial treatment with sitagliptin, metformin, or the combination therapy of sitagliptin and metformin provided substantial and durable glycemic control, improved markers of β-cell function, and was generally well-tolerated over 54 weeks in patients with type 2 diabetes.