Treatment Of Type 2 Diabetes Mellitus Patients Research Articles

Health economic evaluation of dipeptidyl peptidase-4 inhibitors

Sir, The predicted loss of national income from diabetes in India is 336.6 billion International Dollars.[1] Furthermore, studies have demonstrated that the prevalence of diabetes in India is rising with the progression of time.[2] Therefore, this financial burden is bound to increase. About 90-95% of all the diabetes patients are of the type-2 diabetes mellitus (T2DM). A range of classes of oral therapeutic agents exists for the treatment of T2DM. Among these classes, the newest US FDA-approved drug therapeutic class is of the DPP-4 inhibitors. DPP-4 inhibitors offer substantial glycemic control in T2DM patients. However, DPP-4 inhibitors come at increased costs. Thus a systematic review of the health economic evaluation of DPP-4 inhibitors is required. Separately, the PubMed was searched using the following search strategies: (1) (“saxagliptin” [Supplementary Concept]) AND “Economics”[Mesh] 2) (“sitagliptin” [Supplementary Concept]) AND “Economics”[Mesh] 3) (“vildagliptin” [Supplementary Concept]) AND “Economics”[Mesh] 4) (“BI 1356” [Supplementary Concept]) AND “Economics”[Mesh]. The references cited in all the above retrieved publications were also reviewed for relevance and were obtained and included in the search results when applicable. Currently, saxagliptin is approved at once a daily dosage of 2.5 mg and 5 mg in individuals with normal renal functioning and at 2.5 mg in individuals with moderate-to-severe renal insufficiency or end-stage renal disease (ESRD).[3,4] Furthermore, several clinical trials have shown the effectiveness, safety, and tolerability of saxagliptin in terms of HbA1C, FPG, and PPG reductions.[3,4] A total of three studies were obtained when the PubMed was searched for saxagliptin and economics, combined. These searches were examined as follows. The abstracts of these three studies were reviewed for the inclusion criterion of the cost-effectiveness analysis of saxagliptin. This lead to non-inclusion of all three studies, as none of them met the above described inclusion criterion. This indicates that, including India, no health economic evaluation of saxagliptin has been conducted till date in any part of the world. Currently, the recommended daily dosage of sitagliptin is 100 mg once daily which may be taken without regard to food.[4] The efficacy, safety, and tolerability of sitagliptin is well established in several well designed clinical trial studies.[4] A total of 11 studies were obtained when the PubMed was searched for sitagliptin and economics, combined. The articles obtained were examined for the inclusion criterion of the health economic evaluation of sitagliptin. Based on this criterion, only one study evaluating the cost and consequences associated with sitagliptin was found.[5] As per this study, in comparison to glyburide and exenatide, sitagliptin was found cost-effective. Nonetheless, this study was conducted in the United States settings, and, therefore, the results of cost-effectiveness analysis, if conducted in any other country, may differ. No other study evaluating the pharmacoeconomics of sitagliptin was found in the conducted literature search. Vildagliptin is currently not approved by the US FDA, but is in India, European countries, and Japan for the treatment of T2DM patients. Currently, vildagliptin is given 50 mg twice a day in combination with metformin or a thazolidinedione and 50 mg once a day in combination with sulfonylurea.[6] The efficacy, safety, and tolerability of vildagliptin have been established in various clinical trials of durations of 12 to 104 weeks.[6] Only one study was found when PubMed was searched for vildagliptin and economics, combined. The full-text article for this study was retrieved and was reviewed for the health economic evaluation of vildagliptin.[4] On reviewing the full-text article, no health economic evaluation of vildagliptin was found. This indicates that, including India, no health economic evaluation of vildagliptin has been conducted in any part of the world till date. Currently, the recommended dose of linagliptin (BI 1356) is 5 mg once a day, with or without food. No active-comparator clinical trial study of linagliptin monotherapy has been conducted till now. However, in two double-blinded, placebo-controlled clinical trials, the efficacy, safety, and tolerability of linagliptin was established.[7] No studies were found when PubMed was searched for linagliptin (BI 1356) and economics, combined. This indicates that no health economic evaluation of linagliptin has been conducted till date in any part of the world. Sitagliptin, saxagliptin, vildaglitpin, and linagliptin have been approved worldwide including in places such as India, USA, and Europe. However, this literature review demonstrates that, except for sitagliptin, no formal economic evaluation of DPP-4 inhibitors has been conducted till date in any part of the world. For sitagliptin also, only one cost-effectiveness analysis conducted in the US settings was found. Therefore, formal and systematic health economic evaluations for assessing the cost-effectiveness of DPP-4 inhibitors in the treatment of T2DM are required in India as well as in other parts of the world.

Dapagliflozin: more than just another oral glucose-lowering agent?

Importance of the field: With current hypoglycemic therapies, only half of type 2 diabetes mellitus (T2DM) patients achieve optimal glycemic control and even fewer maintain it. Therefore, there is an unmet need for novel antidiabetic agents. Dapagliflozin, a selective inhibitor of sodium glucose transporter 2 (SGLT2), targets hyperglycemia independently of insulin, via decreasing renal glucose reabsorption.Areas covered in this review: We critically assess the results of up-to-date clinical trials with dapagliflozin in patients with T2DM and discuss its potential therapeutic applications.What the reader will gain: Dapagliflozin, apart from targeting hyperglycemia, also exerts beneficial effects on blood pressure, lipid profile, body weight and waist circumference. Furthermore, serum uric acid and high sensitivity C-reactive protein levels were decreased in dapagliflozin-treated patients. However, there are also potentially negative effects related to dapagliflozin use that need to be addressed, such as increased hematocrit and serum parathyroid levels and the possibility of a higher rate of urinary tract and genital infections.Take home message: The use of dapagliflozin in the treatment of T2DM patients seems promising but more evidence is needed.

Evaluation of the weight‐increasing effects of biphasic analog and regular NPH insulin mixtures in patients with Type 2 diabetes mellitus

Weight gain is a significant problem in diabetic patients in terms of worsening glycemic control, increasing diabetic and cardiovascular morbidity and mortality, and contributing to social and psychological problems. In the present study, we evaluated the effects of a biphasic analog and regular NPH insulin mixtures on weight gain in patients with Type 2 diabetes mellitus (T2DM) over 1 year. Group I consisted of 71 patients (29 men and 42 women) being treated with analog mixtures (insulin lispro 75/25 mix and biphasic insulin aspart 70/30 mix) twice daily; Group II consisted of 69 patients (23 men and 46 women) being treated with a regular insulin mixture (70/30) twice daily. Starting weight, body mass index, HbA1c, and hypoglycemic episodes were evaluated after 6 and 12 months. Weight gain in Group I at 6 and 12 months was 1.41 ± 2.70 and 2.08 ± 3.74 kg, respectively. In Group II, weight gain at 6 and 12 months was 1.5 ± 3.0 and 2.29 ± 3.85 kg, respectively. Intragroup comparisons indicated that, for both groups, weight gain at 6 and 12 months differed significantly from the starting weight. However, no significant differences in weight gain were found between the two groups (P > 0.05). The weight-increasing effects of an analog mixture of insulin and the NPH regular mixture of insulin appear to be similar. This should be taken into account when determining the type of insulin to use in treating T2DM patients.

A Model for Glucose, Insulin, and Beta‐Cell Dynamics in Subjects With Insulin Resistance and Patients With Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) is a progressive, metabolic disorder characterized by reduced insulin sensitivity and loss of beta-cell mass (BCM), resulting in hyperglycemia. Population pharmacokinetic-pharmacodynamic (PKPD) modeling is a valuable method to gain insight into disease and drug action. A semi-mechanistic PKPD model incorporating fasting plasma glucose (FPG), fasting insulin, insulin sensitivity, and BCM in patients at various disease stages was developed. Data from 3 clinical trials (phase II/III) with a peroxisome proliferator-activated receptor agonist, tesaglitazar, were used to develop the model. In this, a modeling framework proposed by Topp et al was expanded to incorporate the effects of treatment and impact of disease, as well as variability between subjects. The model accurately described FPG and fasting insulin data over time. The model included a strong relation between insulin clearance and insulin sensitivity, predicted 40% to 60% lower BCM in T2DM patients, and realistic improvements of BCM and insulin sensitivity with treatment. The treatment response on insulin sensitivity occurs within the first weeks, whereas the positive effects on BCM arise over several months. The semi-mechanistic PKPD model well described the heterogeneous populations, ranging from nondiabetic, insulin-resistant subjects to long-term treated T2DM patients. This model also allows incorporation of clinical-experimental studies and actual observations of BCM.

Reduced serum resistin levels in diabetic patients: Study from western India

Objective Resistin is an adipocyte-derived peptide that might play a role in obesity and insulin resistance (IR); however, its role in humans is largely unknown. The aim of the study was to elucidate the role of serum resistin and explore its relationship with inflammatory marker C-reactive protein (CRP) and adipocytokine (leptin, adiponectin) in Indian diabetic patients. Design and methods A total of 171 subjects including 41 controls, 41 obese and 89 Type 2 diabetes mellitus (T2DM) patients were recruited in this cross-sectional study. Fasting serum resistin, leptin, adiponectin, insulin and CRP were measured by enzyme immunoassay. The relation between these variables was studied by univariate and multiple regression analysis. Results Serum resistin levels were significantly reduced in non-obese treated T2DM patients. In the correlation analysis after controlling for age and BMI we found that resistin is significantly associated with leptin (0.687, p < 0.002) and CRP (0.549, p < 0.018) in only control females and with CRP (0.642, p < 0.01) in T2DM female patients. In multiple linear regression analysis resistin was independently predicted by the leptin ( p < 0.01) and leukocyte ( p < 0.004) in controls, treated T2DM patients. Conclusion Reduced resistin and leptin levels in non-obese treated T2DM and significant association between these two in control and treated T2DM suggest interplay between these two adipocytokines. In addition, the weak association of resistin with diabetes indicates that it may be playing an indirect role in the pathogenesis of T2DM.

Pioglitazone versus rosiglitazone treatment in patients with type 2 diabetes and dyslipidemia: cost-effectiveness in the US

ABSTRACTObjectives: Pioglitazone hydrochloride (Actos) and rosiglitazone maleate (Avandia) are members of the thiazolidinedione (TZD) class of oral anti-diabetic drugs (OADs) and are used to treat type 2 diabetes mellitus (T2DM). Greater beneficial effects on lipids have been demonstrated with pioglitazone, however. Study objectives were to evaluate the long-term cost-effectiveness of pioglitazone compared to rosiglitazone in treating patients with T2DM and dyslipidemia, and determine the extent to which reported beneficial lipid effects of pioglitazone would improve clinical and economic outcomes through reduced macrovascular complications.† Actos is a trade name of Takeda Pharmaceuticals Co. Ltd., Deerfield, IL, US‡ Avandia is a trade name of GlaxoSmithKline, Research Triangle, NC, USResearch design and methods: The validated CORE Diabetes Model (CDM) was used to simulate changes in glycosylated hemoglobin (HbA1c), complications, and direct medical costs. Baseline parameters came from a multi-center, double-blind trial comparing lipid and glycemic effects of pioglitazone (n = 400) and rosiglitazone (n = 402) among individuals with T2DM and untreated dyslipidemia. Sensitivity analyses examined the impact of cohort, clinical, and cost inputs on incremental cost effectiveness ratios (ICERs).Results: In the base case, pioglitazone was associated with mean (standard deviation [SD]) quality-adjusted life years (QALYs) of 7.476 (0.123) vs. 7.326 (0.128) for rosiglitazone. Pioglitazone had $3038 higher total direct costs, but $580 lower complication costs. Risks of four cardiovascular complications were reduced with pioglitazone (relative risks 0.860–0.942), while risks of 17 other complications were slightly higher (relative risks 1.001–1.056). The ICER for pioglitazone treatment was $20 171/QALY. Results were most sensitive to the effects of HbA1c, high-density lipoprotein-cholesterol, overall lipid effects, and pioglitazone acquisition costs.Conclusions: Study limitations include issues of generalizability of the trial patient population, as well as inability to capture non-adherence and variation in ‘real-world’ treatment patterns. Nevertheless, pioglitazone (when compared to rosiglitazone) was found to have long-term value as a treatment option for T2DM patients with dyslipidemia treated within the US payer setting.

Incretin Mimetics and DPP-IV Inhibitors: New Paradigms for the Treatment of Type 2 Diabetes

Incretin mimetics are a new class of pharmacological agents with multiple antihyperglycemic actions that mimic several of the actions of incretin hormones originating in the gut, such as glucagon-like peptide (GLP)-1. Dipeptidyl peptidase-IV (DPP-IV) inhibitors suppress the degradation of many peptides, including GLP-1, thereby extending their bioactivity. These agents seem to have multiple mechanisms of action for the treatment of type 2 diabetes mellitus (T2DM), including some or all the following: enhancement of glucose-dependent insulin secretion, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying, and decreased food intake. Exenatide (BYETTA) is the first incretin mimetic approved for clinical use by the US Food and Drug Administration. In phase 3 clinical trials, exenatide reduced HbA(1c) by approximately 1% and body weight by approximately 2 kg in T2DM patients failing to achieve glycemic control with metformin and/or a sulfonylurea, with mild-to-moderate nausea the most common side effect. Several GLP-1 analogues and DPP-IV inhibitors are in late-stage clinical testing and may soon become available for treating T2DM patients. The use of these agents may provide an opportunity to bring about new improvements in diabetes care.