Oral Antihyperglycemic Medications Research Articles

Assessing the cost-effectiveness of a once-weekly GLP-1 analogue versus an SGLT-2 inhibitor in the Spanish setting: Once-weekly semaglutide versus empagliflozin

Aims: Controlling costs while maximizing healthcare gains is the predominant challenge for healthcare providers, and therefore cost-effectiveness analysis is playing an ever-increasing role in healthcare decision making. The aim of the present analysis was to assess the long-term cost-effectiveness of subcutaneous once-weekly semaglutide (0.5 mg and 1 mg) versus empagliflozin (10 mg and 25 mg) in the Spanish setting for the treatment of patients with type 2 diabetes (T2D) with inadequate glycemic control on oral anti-hyperglycemic medications.Material and methods: The IQVIA CORE Diabetes Model was used to project outcomes over patient lifetimes with once-weekly semaglutide versus empagliflozin, with treatment effects based on a network meta-analysis. The analysis captured treatment costs, costs of diabetes-related complications, and the impact of complications on quality of life, based on published sources. Outcomes were discounted at 3.0% per annum.Results: Once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in discounted quality-adjusted life expectancy of 0.12 and 0.15 quality-adjusted life years (QALYs), respectively, versus empagliflozin 10 mg and improvements of 0.11 and 0.14 QALYs, respectively, versus empagliflozin 25 mg. Treatment costs were higher with once-weekly semaglutide compared with empagliflozin, but this was partially offset by cost savings due to avoidance of diabetes-related complications. Once-weekly semaglutide 0.5 mg and 1 mg were associated with incremental cost-effectiveness ratios of EUR 2,285 and EUR 161 per QALY gained, respectively, versus empagliflozin 10 mg, and EUR 3,090 and EUR 625 per QALY gained, respectively, versus empagliflozin 25 mg.Conclusions: Based on a willingness-to-pay threshold of EUR 30,000 per QALY gained, once-weekly semaglutide 0.5 mg and 1 mg were projected to be cost-effective versus empagliflozin 10 mg and 25 mg for the treatment of patients with T2D with inadequate glycemic control on oral anti-hyperglycemic medications in the Spanish setting, irrespective of patients’ BMI at baseline.

Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors: A Clinician's Guide.

This comprehensive review covers the historical background, physiology, application in type 2 diabetes, novel uses, cardiovascular benefits, side effects and contraindications of sodium-glucose cotransporter-2 (SGLT2) inhibitors. SGLT2 inhibitors are an insulin-independent class of oral antihyperglycemic medication that clinicians use in the treatment of type 2 diabetes. Multiple landmark clinical trials support the effectiveness of SGLT2 inhibitors in reducing blood glucose levels, but it is important to understand when to properly utilize them. SGLT2 inhibitors are the most beneficial as an adjunct medication in addition to metformin in patients with a history of cardiovascular or renal disease who need further hemoglobin A1c reduction. The novel mechanism of action also demands clinicians be aware of the side effects not typically experienced with other oral antihyperglycemic drugs, such as genital tract infections, lower leg amputations, electrolyte disturbances and bone fractures. On top of their benefits in type 2 diabetes, novel uses for SGLT2 inhibitors are being uncovered. Diabetic patients with non-alcoholic fatty liver disease, who are at an increased risk of cirrhosis and hepatocellular carcinoma, experience a clinically significant reduction in serum alanine aminotransferase levels. SGLT2 inhibitors are also effective at lowering body weight in obese individuals and decreasing systolic blood pressure. Dual SGLT1/SGLT2 inhibitors are currently being investigated as possibly the first oral medication for type 1 diabetes.

Sodium-glucose co-transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol.

Recent phase 3 clinical trials have evaluated the impact of adding sodium-glucose co-transporter (SGLT) inhibitors to the type 1 diabetes armamentarium. These trials studied SGLT2 inhibitors (dapagliflozin and empagliflozin) and a dual SGLT1 and SGLT2 inhibitor (sotagliflozin), and demonstrated that these oral non-insulin antihyperglycaemic medications are able not only to improve glycaemic control, but also to reduce body weight and extend time in range without increasing rates of hypoglycaemia in type 1 diabetes. Diabetic ketoacidosis (DKA) is a feature of type 1 diabetes and the risk is increased when SGLT inhibitors are used in type 1 diabetes. To minimize the risk of DKA and still gain the multiple benefits, we developed the "STOP DKA Protocol ", an easily accessible and practical tool, that provides a risk mitigation strategy for reducing DKA in patients with type 1 diabetes being treated with SGLT inhibitors.

Efficacy and Safety of Dulaglutide Versus Insulin Glargine in Chinese T2DM Patients: A Subgroup Analysis of a Randomized Trial (AWARD-CHN2).

IntroductionTo evaluate efficacy and safety data of dulaglutide in Chinese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with 1–2 oral antihyperglycemic medications (OAMs).MethodsThis is a subgroup analysis of a phase 3, open-label, randomized, parallel-arm, 52-week study in Chinese patients aged ≥ 18 years with T2DM who had inadequate glycemic control with OAMs (glycated hemoglobin [HbA1c] ≥ 7.0% and ≤ 11.0%). The primary endpoint was assessment of the noninferiority of dulaglutide 1.5 mg as measured by change in HbA1c, compared with insulin glargine (glargine), using a 0.4% noninferiority margin at week 26.ResultsA total of 607 patients from China were randomized 1:1:1 to once-weekly dulaglutide 1.5 or 0.75 mg or once-daily glargine. At week 26, the least squares mean (LSM) change from baseline in HbA1c was greater with dulaglutide 1.5 mg (− 1.67%) and dulaglutide 0.75 mg (− 1.31%) compared with glargine (− 1.11%). The LSM (95% confidence interval) for the difference of dulaglutide 1.5 mg and 0.75 mg vs glargine was − 0.56% (− 0.75 to − 0.37) and − 0.20% (− 0.39 to − 0.01), respectively. Both doses of dulaglutide were noninferior and superior to glargine at 26 weeks and 52 weeks (two-sided P value < 0.05). The mean body weight decreased (P < 0.001) and total hypoglycemia rates were lower (P < 0.05) in the dulaglutide groups compared with the glargine group. Gastrointestinal adverse events (AEs) were the most frequently reported AEs in dulaglutide groups.ConclusionBoth doses of dulaglutide are efficacious and tolerable in Chinese patients with T2DM who had inadequate glycemic control on OAMs.Trial RegistrationClinicalTrials.gov identifier, NCT01648582.FundingEli Lilly and Company.Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-019-0646-y) contains supplementary material, which is available to authorized users.

Use of Insulin Glargine 100U/mL for the Treatment of Type 2 Diabetes Mellitus in East Asians: A Review.

Insulin glargine (IGlar) 100 U/mL (IGlar-100) is widely used in East Asian countries for the treatment of type 2 diabetes mellitus (T2DM) and is the gold standard of basal insulin treatment. In this review we summarize key information about clinical experience with IGlar-100 in East Asian patients with T2DM, including findings from clinical trials and postmarketing studies. We also provide recommendations and opinions on the optimal use of IGlar-100 in this population. The findings from the studies highlighted in our review indicate that IGlar-100 can be a suitable treatment option for East Asians with T2DM, from initial therapy in combination with oral antihyperglycemic medications through to different combinations and intensification models.FundingEli Lilly and Company.

Recent advances in diabetes treatments and their perioperative implications.

Purpose of reviewThe implications for perioperative management of new oral antihyperglycemic medications and new insulin treatment technologies are reviewed.Recent findingsThe preoperative period represents an opportunity to optimize glycemic control and potentially to reduce adverse outcomes. There is now general consensus that the optimal blood glucose target for hospitalized patients is approximately 106–180 mg/dl (6–10 mmol/l). Recommendations for the management of antihyperglycemic medications vary among national guidelines. It may not be necessary to cease all antihyperglycemic agents prior to surgery. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with higher rates of ketoacidosis especially in acutely unwell and postsurgical patients. The clinical practice implications of new insulin formulations, and new systems for insulin delivery, are not clear. The optimal perioperative management of these will vary depending on local institutional factors such as staff skills and existing clinical practices. Improved hospital care delivery standards, quality assurance, process improvements, consistency in clinical practice, and coordinated multidisciplinary teamwork should be a major focus for improving outcomes of perioperative patients with diabetes.SummarySulfonylureas and SGLT2i should be ceased before moderate or major surgery. Other oral antihyperglycemic therapies may be continued or ceased. Complex patients and/or new therapies require specialized multidisciplinary management.

Lilly Insulin Glargine Versus Lantus® in Insulin-Naïve and Insulin-Treated Adults with Type 2 Diabetes: A Randomized, Controlled Trial (ELEMENT 5).

IntroductionThis study compared the efficacy and safety of similar U-100 insulin glargine products, namely, Lilly insulin glargine (LY IGlar; Basaglar®) and the reference insulin glargine product (IGlar; Lantus®), used once daily in combination with oral antihyperglycemic medications (OAMs) in adults with type 2 diabetes (T2D).MethodsELEMENT 5 was a phase III, randomized, multinational, open-label, treat-to-target, 24-week trial. Participants were insulin naïve (glycated hemoglobin [HbA1c] ≥ 7.0% to ≤ 11.0%) or on basal insulin (IGlar, neutral protamine Hagedorn or insulin detemir; HbA1c ≤ 11.0%) and taking ≥ 2 OAMs. The primary objective was to show that LY IGlar is noninferior to IGlar in terms of HbA1c reduction (0.4% noninferiority margin).ResultsThe study population (N = 493) was predominantly Asian (48%) or White (46%), with similar baseline characteristics between arms (P > 0.05). At 24 weeks, LY IGlar was noninferior to IGlar in terms of change in HbA1c level from baseline (− 1.25 vs. − 1.22%, respectively; least squares mean difference − 0.04%; 95% confidence interval − 0.22%, 0.15%). Other 24-week efficacy and safety results were also similar between treatments (P > 0.05), including insulin dose; percentage of patients having HbA1c of < 7% and ≤ 6.5%; overall rate and incidence of total, nocturnal, and severe hypoglycemia; adverse events; insulin antibody response; and weight gain. Daily mean 7-point self-monitored blood glucose reduction was similar between treatments at 24 weeks, with no differences at any time point except premorning-meal (fasting) blood glucose (LY IGlar − 2.37 mmol/L; IGlar − 2.69 mmol/L; P = 0.007).ConclusionOverall, LY IGlar and IGlar combined with OAMs provided similar glucose control and safety findings in this T2D population, which included a greater proportion of Asian patients and had broader background basal insulin experience than a previously studied T2D population.Trial RegistrationClinicalTrials.gov identifier, NCT02302716.FundingEli Lilly and Company and Boehringer Ingelheim.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0549-3) contains supplementary material, which is available to authorized users.

Effects of short-term combination therapy with insulin on glycoregulation and insulin secretory function in patients with type 2 diabetes mellitus and secondary failure to treatment with oral antidiabetic agents

&amp;lt;p&amp;gt;Introduction. Secondary failure to treatment with oral antidiabetic agents is defined as the absence of a favorable reaction to the oral therapy which had proved effective in the previous course of the treatment. The aim of the study is to investigate the residual effects of the short-term combination therapy with insulin on glycoregulation and insulin secretory function. Methods. The sample comprised 53 patients with type 2 diabetes mellitus (DM2) and secondary failure to treatment with oral antidiabetic agents who had been receiving combination therapy (basal insulin plus metformin) for three months. Following the evaluation of acute effects of insulin therapy, the patients had been receiving oral antihyperglycemic medications, used at the time of secondary failure, for three months, after which the residual effects of insulin therapy were estimated. Results. Three-month combination therapy significantly improved glycoregulation (fasting glycemia: 9.4 mmol/l vs. 6.1 mmol/l; postpransial glycemia: 11.5 mmol/l vs. 7.3mmol/l; daily glycemic profile: 10.0 mmol/l vs. 7.2 mmol/l) and insulin secretory parameters (insulinemia: 16.63 mU/l vs. 10.8 mU/l; C-peptid: 1.53 mg/ml vs. 1.81 mg/ml) compared with the period when secondary failure to oral therapy was observed (acute effects). Three months after the insuline therapy, glycoregulation and insulin secretory function were slightly poorerresidual effects (glycemia: 7.1mmol/l; postpransial glycemia: 8.3 mmol/l; daily glycemic profile: 8.4mmol/l; insulinemia: 13.3mU/l; C-peptid: 1.72 mg /ml). Conclusion. The reinclusion of oral antidiabetic agents after short-term insulin therapy led to mild deterioration in insulin secretory function. Nevertheless, all observed parameters of metabolic status were significantly better compared with the period prior to short-term use of insulin.&amp;lt;/p&amp;gt;

Use of SGLT-2 Inhibitors in Patients With Type 1 Diabetes Mellitus.

Introduction: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are the newest class of oral antihyperglycemic medications approved for the treatment of type 2 diabetes mellitus (DM2). Although they are not approved for use in type 1 diabetes mellitus (DM1), SGLT2 inhibitors may help DM1 patients achieve their HbA1c goals by decreasing their insulin requirements, without inducing hypoglycemic episodes and weight gain. Methods: We conducted a retrospective chart review of 26 patients with DM1 treated with off-label SGLT-2 inhibitors. The primary objective was change in HbA1c and weight. The secondary objective was assessing the effect on insulin requirements, blood pressure, and lipid profile. Results: Improvement in HbA1c level was seen in 20 of the 26 patients (77%) after initiation of SGLT-2 inhibitors. The average decrease in HbA1c was 0.32% (P = .032), with changes seen as early as 1 month posttherapy and maintained with continued SGLT-2 inhibitor use. There was a trend toward weight loss that was not significant. No significant changes in blood pressure or lipid profiles were seen except for a slight increase in low-density lipoprotein (P = .049). No patient developed euglycemic diabetic ketoacidosis. Three patients discontinued therapy due to uncontrolled genital yeast infections. Conclusion: SGLT-2 inhibitors can be a useful adjunctive therapy in patients with DM1 to improve glycemic control and weight. Although our study did not show any significant changes in the metabolic profile and insulin requirements in these patients, a larger sample size may yield different results.

Impact of type 2 diabetes mellitus on short- and long-term mortality after coronary artery bypass surgery

BackgroundType 2 diabetes mellitus (DM) is a frequent co-morbidity among patients undergoing coronary artery bypass grafting (CABG) surgery. The aim of this study was to evaluate the impact of DM on the early- and long-term outcomes of patients who underwent isolated CABG.MethodsWe performed an observational cohort study in a large tertiary medical center over a period of 11 years. All data from patients who had undergone isolated CABG surgery between 2004 and 2014 were obtained from our departmental database. The study population included 2766 patients who were divided into two groups: Group I (1553 non-diabetic patients), and Group II (1213 patients suffering from type 2 DM). Group II patients were then divided into two subgroups: subgroup IIA (981 patients treated with oral antihyperglycemic medications) and subgroup IIB (232 insulin-treated patients with or without additional oral antihyperglycemic drugs). In-hospital, 1-, 3-, 5- and 10-year mortality outcome variables were evaluated. Mean follow-up was 97 ± 41 months.ResultsIn-hospital mortality was similar between Group I and Group II patients (1.87% vs. 2.31%, p = 0.422) and between the subgroups IIA and IIB (2.14% vs. 3.02%, p = 0.464). Long-term mortality (1, 3, 5 and 10 years) was higher in Group II (DM type 2) compared with Group I (non-diabetic patients) (5.3% vs. 3.6%, p = 0.038; 9.3% vs. 5.6%, p < 0.001; 15.3% vs. 9.3%, p < 0.001 and 47.3% vs. 29.6% p < 0.001). Kaplan–Meier analysis demonstrated that all-cause mortality was higher in Group II compared with Group I (p < 0.001) and in subgroup IIB compared with subgroup IIA (p = 0.001). Multivariable analysis showed that DM increased the mortality hazard by twofold, and among diabetic patients, insulin treatment increased the mortality hazard by twofold.ConclusionsDiabetic and non-diabetic patients have similar in-hospital mortality rates. Survival rates of diabetic patients start to deteriorate 3 year after surgery. Type 2 DM is an independent predictor for long-term mortality after isolated CABG surgery. Mortality is even higher when the diabetes treatment strategy included insulin.

Blood glucose profiles in East Asian and Caucasian injection-naive patients with type 2 diabetes inadequately controlled on oral medication: a pooled analysis.

AimThe primary objective of this study was to compare blood glucose (BG) excursions between East Asian and Caucasian patients with type 2 diabetes mellitus (T2DM) who were injection‐naive, had inadequate glycemic control with oral antihyperglycemic medications, and who required initiation with injectable therapy.MethodsThis retrospective pooled analysis included individual patient data from completed clinical trials (Insulin lispro injection/dulaglutide development programs, first patient visit ≥1997). All included patients were ≥18 years, were East Asian or Caucasian, and had data for self‐monitored BG at baseline. The primary outcome, BG excursion at baseline (least‐squares mean, standard error), was compared between patient groups using an analysis of covariance with race as the fixed effect. Independent covariates included baseline body weight, baseline HbA1c, age, and duration of T2DM.ResultsCaucasian (n = 6779) and East Asian (n = 1638) patients from 21 trials were included. BG excursions were significantly higher for East Asian than Caucasian patients at breakfast (4.03 [0.075] vs 2.59 [0.045] mmol/L), lunch (3.37 [0.080] vs 1.43 [0.049] mmol/L), and dinner (3.16 [0.080] vs 1.74 [0.047] mmol/L) (P < 0.001 adjusted analyses). Similar findings were observed for the unadjusted analyses. At each time point, postprandial BG was significantly higher for East Asian than Caucasian patients (with adjusted and unadjusted analyses).ConclusionThese findings suggest that BG excursion and postprandial BG are higher among East Asian patients with T2DM than Caucasian patients. In addition, these findings may help clinicians select appropriate treatments for East Asian patients with T2DM who require injection therapy.

The Prevalence and Impact of Diabetes Mellitus among Undocumented Immigrants in an Indigent Care Program in Riverside, California

Background: Acculturated undocumented immigrants (UI) in the U.S. with sedentary lifestyle and poor eating habits are at risk for diabetes mellitus (DM). UI also face adverse social, economic, and psychological stressors that may lead to poor clinical outcomes. No study to date has assessed DM prevalence and clinical outcomes among UI. Methods: Riverside University Health System, a county health system, provides medical care for indigent patients including UI. Of 8,466 UI receiving indigent care as of March, 2017, 500 UI were randomly selected to assess DM prevalence and clinical outcomes. Results: The mean age was 46.2 with more females (59%) accessing medical care. Over 95% were Hispanics and 74% were born in Mexico. Most were married and only 11% worked full time. A majority of UI never smoked (67%), and only 18% consumed alcohol. The prevalence of DM was 27%, and diabetics were older than nondiabetics (52.2 vs. 43.9, p&amp;lt;0.001) with comparable BMIs (29.9 vs. 28.9, p=0.12). The mean hemoglobin A1c was 8.3 and insulin and oral anti-hyperglycemic medication use was 8% and 19%, respectively. The total clinic visits among diabetics was 19 compared to 13 in nondiabetics (p=0.018) while total emergency department visits were comparable between two groups (2 vs. 2, p=0.100). The use of prescription medications was higher in diabetics than nondiabetics (7 vs. 4, p=&amp;lt;0.001). Diabetics had a higher rate of hypertension compared to nondiabetics (57% vs. 20%, p&amp;lt;0.001), but other clinical conditions were similar [congestive heart failure (1% vs. 3%), cancer (4% vs. 3%), depression (6% vs. 3%), chronic kidney disease (7% vs. 3%)]. Conclusions: The prevalence of DM among UI is high with poor glycemic control. Diabetics had more clinic visits than nondiabetics and were taking more prescription medications. Despite high prevalence of DM, diabetes-related complication and comorbidity rates were low, which may be due to medical care access through the indigent care program. Disclosure H. Lee: None. B.L. Zakhary: None. M.A. Firek: None. H. Lange: None. C.A. Gomez: None. A. Firek: None.

Reduced Glucose Variability With Glucose-Dependent Versus Glucose-Independent Therapies Despite Similar Glucose Control and Hypoglycemia Rates in a Randomized, Controlled Study of Older Patients With Type 2 Diabetes Mellitus.

Background:Few studies have evaluated continuous glucose monitoring (CGM) in older patients with type 2 diabetes mellitus (T2DM) not using injectable therapy. CGM is useful for investigating hypoglycemia and glycemic variability, which is associated with complications in T2DM.Methods:A CGM substudy of Individualized treatMent aPproach for oldER patIents in a randomized trial in type 2 diabetes Mellitus (IMPERIUM)) was conducted. Patients were vulnerable (moderately ill and/or frail) older (≥65 years) individuals with suboptimally controlled T2DM. Strategy A comprised glucose-dependent therapies (n = 26) with a nonsulfonylurea oral antihyperglycemic medication (OAM) and a glucagon-like peptide-1 receptor agonist as the first injectable. Strategy B comprised non-glucose-dependent therapies (n = 21) with sulfonylurea as the preferred OAM and insulin glargine as the first injectable. Primary endpoints were duration and percentage of time spent with blood glucose (BG) ≤70 mg/dL over 24 hours at week 24.Results:Duration and percentage of time spent with hypoglycemia at ≤70 mg/dL were similar for Strategy A and Strategy B; glycemic control improved similarly in both arms (LSM change in HbA1c at week 24; A = −1.2%, B = −1.4%). Duration and percentage time spent with euglycemia and hyperglycemia were also similar in both arms. However, Strategy A was associated with lower within-day (21.1 ± 1.2 vs 25.1 ± 1.4, P = .046) and between-day (5.4 ± 1.0 vs 9.1 ± 1.3, P = .038) BG variability (coefficient of variance [LSM ± SE]) at week 24.Conclusions:This CGM substudy in older patients with T2DM showed lower within- and between-day BG variability with glucose-dependent therapies but similar HbA1c reductions and hypoglycemia duration with glucose-independent strategies.

The Potential Role of SGLT2 Inhibitors in the Treatment of Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus is a difficult disease to treat due to the relative paucity of therapeutic options other than injectable insulin. The latter, however, can induce hypoglycemia, which has been linked to enhanced cardiovascular risk. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-hyperglycemic medications that do not increase the hypoglycemia risk and are US Food and Drug Administration (FDA) approved in type 2 diabetes mellitus. SGLT2 inhibitors may also be of benefit in type 1 diabetic patients, in addition to insulin, although they have not yet been approved for this indication. By blocking SGLT2 in the early proximal tubules of the kidney, these drugs decrease renal glucose retention, which is enhanced in hyperglycemia, thereby improving blood glucose control, in type 1 and type 2 diabetic patents. Their low hypoglycemia risk is due to the compensating reabsorption capacity of another glucose transporter, SGLT1, in the downstream late proximal tubule and the body's metabolic counter-regulation, which remains intact during SGLT2 inhibition. When insulin dosage is lowered too much, SGLT2 inhibitors can enhance ketogenesis to the extent that the risk of diabetic ketoacidosis increases, particularly in type 1 diabetic patients. SGLT2 inhibitors improve the renal and cardiovascular outcome in type 2 diabetic patients. The mechanisms likely include a reduction in glomerular hyperfiltration, blood pressure, volume overload, and body weight, as well as lowering blood glucose without increasing the hypoglycemia risk. The same mechanistic effects are induced in type 1 diabetic patients. More studies are needed with SGLT2 inhibitors in type 1 diabetic patients, including renal and cardiovascular clinical outcome trials, to fully evaluate their therapeutic potential in this specific population.

A randomised controlled trial of a duodenal-jejunal bypass sleeve device (EndoBarrier) compared with standard medical therapy for the management of obese subjects with type 2 diabetes mellitus

IntroductionThe prevalence of obesity and obesity-related diseases, including type 2 diabetes mellitus (T2DM), is increasing. Exclusion of the foregut, as occurs in Roux-en-Y gastric bypass, has a key role in...

Glycaemic outcomes of an Individualized treatMent aPproach for oldER vulnerable patIents: A randomized, controlled stUdy in type 2 diabetes Mellitus (IMPERIUM)

AimsTo compare the glycaemic outcomes of 2 glucose‐lowering treatment strategies in vulnerable (moderately ill and/or frail) patients aged ≥65 years with type 2 diabetes whose individual HbA1c targets were not met with diet/exercise and/or oral anti‐hyperglycaemic medications (OAMs).MethodsThe primary endpoint of this study was a composite of achieving/maintaining individualized HbA1c targets without “clinically significant” hypoglycaemia (severe hypoglycaemia or repeated hypoglycaemia causing interruption of patients’ activities or blood glucose <54 mg/dL). Strategy‐A comprised glucose‐dependent therapies (n = 99) with a non‐sulphonylurea OAM and a glucagon‐like peptide‐1 receptor agonist as the first injectable. Strategy‐B comprised non‐glucose‐dependent therapies (n = 93) with sulphonylurea as the preferred OAM and insulin glargine as the first injectable.ResultsThere was no significant difference between Strategy‐A and Strategy‐B in percentages of patients achieving the primary endpoint (64.5% vs 54.9%; P = .190). Mean incidences (A vs B) of total (10.2% vs 53.8%), documented symptomatic (5.1% vs 36.6%), and asymptomatic (8.2% vs 32.3%) hypoglycaemia were lower for Strategy‐A (P < .001 each). Proportions of patients achieving/maintaining HbA1c target (A, 63.3% vs B, 55.9%) were similar.ConclusionSimilar proportions of older, vulnerable aged ≥65 years patients with type 2 diabetes achieved/maintained glycaemic treatment goals without clinically significant hypoglycaemia with Strategies A or B. However, Strategy‐A resulted in lower risk of total, documented symptomatic, and asymptomatic hypoglycaemia. These results identify an approach of potential clinical benefit in this age group and will inform future clinical research in older patients with type 2 diabetes.

Simulation-Based Evaluation of Dose-Titration Algorithms for Rapid-Acting Insulin in Subjects with Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Antihyperglycemic Medications.

The purpose of this prospective, model-based simulation approach was to evaluate the impact of various rapid-acting mealtime insulin dose-titration algorithms on glycemic control (hemoglobin A1c [HbA1c]). Seven stepwise, glucose-driven insulin dose-titration algorithms were evaluated with a model-based simulation approach by using insulin lispro. Pre-meal blood glucose readings were used to adjust insulin lispro doses. Two control dosing algorithms were included for comparison: no insulin lispro (basal insulin+metformin only) or insulin lispro with fixed doses without titration. Of the seven dosing algorithms assessed, daily adjustment of insulin lispro dose, when glucose targets were met at pre-breakfast, pre-lunch, and pre-dinner, sequentially, demonstrated greater HbA1c reduction at 24 weeks, compared with the other dosing algorithms. Hypoglycemic rates were comparable among the dosing algorithms except for higher rates with the insulin lispro fixed-dose scenario (no titration), as expected. The inferior HbA1c response for the "basal plus metformin only" arm supports the additional glycemic benefit with prandial insulin lispro. Our model-based simulations support a simplified dosing algorithm that does not include carbohydrate counting, but that includes glucose targets for daily dose adjustment to maintain glycemic control with a low risk of hypoglycemia.

Occurrence and Predictors of Depression and Poor Quality of Life among Patients with Type-2 Diabetes: A Northern India Perspective.

Background and Aims:Globally, depression has been linked to Type-2 diabetes mellitus (T2DM). However, similar data from India are scant. This study evaluated the occurrence and predictors of depression and health-related quality of life (QOL) in patients with T2DM as compared to healthy controls.Materials and Methods:One hundred adults with T2DM without prior diagnosis of depression and 100 matched controls were evaluated. Depression was assessed using Patient Health Questionnaire-9. World Health Organization QOL Brief (WHO-QOL-BREF) was used to assess QOL. Demography, anthropometry, biochemical parameters of diabetes control, and microvascular and macrovascular complications in patients were recorded.Results:Depression was significantly more common in T2DM (63%) as compared to controls (48%) (odds ratio [OR] – 1.84 [1.04, 3.24]; P = 0.03). In T2DM, depression was higher in patients with disease duration >5 years (OR = 2.66; P = 0.02), glycated hemoglobin >7% (OR = 3.45; P = 0.004), retinopathy (OR – 3.56; P = 0.03), and nephropathy (OR – 4.11; P = 0.07). Occurrence of depression was significantly higher among the patients with macrovascular complications, namely, coronary artery disease (17.4%; P = 0.000006), cerebrovascular disease (14.2%; P = 0.0006), and peripheral vascular disease (7.9%; P = 0.05). Insulin users had higher depression as compared to patients using only oral antihyperglycemic medications (P = 0.034). Patient with depression had significantly low QOL. The WHO-QOL for all the domains was significantly lower in T2DM with microvascular and macrovascular complications, as compared to those without.Conclusion:Indian T2DM had higher prevalence of depression and lower QOL as compared to controls, which was associated with poor glycemic control and higher end-organ damage. Public health measures are required to create more awareness for managing depression in diabetes.

One-year adherence to oral antihyperglycemic medication and risk prediction of patient outcomes for adults with diabetes mellitus: An observational study.

Medication adherence is essential in preventing adverse intermediate outcomes, but little is known on hard outcomes. The aims of this study were to determine the 1-year adherence to oral antihyperglycemic drugs (OADs) and to predict the risk of subsequent health outcomes among (non)adherent patients with diabetes.Using a large Swiss healthcare claims database from 2011 to 2014, we identified all patients aged ≥18 years with diabetes and treated with at least 1 OAD prescription. Adherence to OADs was measured as the proportion of days covered (PDC) over 1 year and subdivided into 2 categories: adherent (PDC ≥ 80%), nonadherent (PDC < 80%). We estimated the relative risk of hospitalization and mortality at follow-up using multivariate Cox proportional hazard models.Based on a sample of 26,713 patients, adherence to OADs was quite low: 42% of the patients achieved a PDC of ≥80% during the 1-year observation period. A 7% reduction in the hospitalization risk and a 10% reduction in the risk of mortality could be observed in adherent patients compared to nonadherent patients (hazard ratio [HR], 0.93 [95% CI, 0.89-0.97]; HR, 0.90 [95% CI, 0.82-0.99]). Subgroup analysis showed that an intensified diabetes therapy had no significant influence on the risk of both outcomes in adherent patients.Poor medication adherence increases the risk of subsequent hospitalizations and premature mortality in patient with diabetes, regardless of disease severity and comorbidities. This emphasizes the need for an earlier identification of patients with poor medication adherence. The awareness of physicians and patients regarding the importance of adherence in diabetes treatment should be increased.

Missed doses of oral antihyperglycemic medications in US adults with type 2 diabetes mellitus: prevalence and self-reported reasons

Background: Adherence to antihyperglycemic medication is thought to be suboptimal, but the proportion of patients missing doses, the number of doses missed, and reasons for missing are not well described. This survey was conducted to estimate the prevalence of and reasons for missed doses of oral antihyperglycemic medications among US adults with type 2 diabetes mellitus, and to explore associations between missed doses and health outcomes.Methods: The study was a cross-sectional patient survey. Respondents were contacted via a commercial survey panel and completed an on-line questionnaire via the Internet. Respondents provided information about their use of oral antihyperglycemic medications including doses missed in the prior 4 weeks, personal characteristics, and health outcomes. Weights were calculated to project the prevalence to the US adult population with type 2 diabetes mellitus. Outcomes were compared according to number of doses missed in the past 4 weeks using bivariate statistics and generalized linear models.Results: Approximately 30% of adult patients with type 2 diabetes mellitus reported missing or reducing ≥1 dose of oral antihyperglycemic medication in the prior 4 weeks. Accidental missing was more commonly reported than purposeful skipping, with forgetting the most commonly reported reason. The timing of missed doses suggested respondents had also forgotten about doses missed, so the prevalence of missed doses is likely higher than reported. Outcomes were poorer among those who reported missing three or more doses in the prior 4 weeks.Conclusions: A substantial number of US adults with type 2 diabetes mellitus miss doses of their oral antihyperglycemic medications.