Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

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 therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Treatment of type 2 diabetes mellitus.

Although most patients with type 2 diabetes mellitus can be initially managed with diet and exercise alone, most eventually require at least oral agents if not insulin to maintain glycemic control. Appropriate therapeutic regimens may be difficult to design, given the diversity of drugs available for clinical use. Physicians must consider not only glycemic control, but also patient preference, concomitant medical conditions, and cost when designing therapeutic regimens

Emerging care for type 2 diabetes: using insulin to reach lower glycemic goals.

Intensive control of blood glucose reduces the incidence and progression of many of the complications of type 2 diabetes. Newer insulin formulations that approach normal physiologic patterns have made it possible to achieve glycemic goals without excessive hypoglycemia

Insulin analogues: new therapies for type 2 diabetes mellitus.

Insulin therapy is ultimately necessary for the control of blood glucose in a majority of patients with type 2 diabetes mellitus. Unfortunately, the pharmacokinetic characteristics of previously available rapid-, intermediate-, and long-acting preparations make sustained normoglycemia almost impossible. Advances in molecular genetic engineering have made possible the development of insulin analogues with pharmacokinetics that more closely mimic the needs of patients with type 2 diabetes. In the following article, we explore the insulin analogues currently available for clinical use, their pharmacokinetics, and the rationale for their use in the treatment of type 2 diabetes, and follow-up with a brief examination of future developments

Basal insulin therapy in type 2 diabetes.

Patients with type 2 diabetes mellitus are usually treated initially with oral antidiabetic agents, but as the disease progresses, most patients eventually require insulin to maintain glucose control. Optimal insulin therapy should mimic the normal physiologic secretion of insulin and minimize the risk of hypoglycemia. This article discusses the role of insulin therapy in patients with type 2 diabetes, emphasizing long-acting insulin agents designed to approximate physiologic basal insulin secretion and provide control over fasting plasma glucose. Clinical trials of recently developed long-acting insulins are reviewed herein, with emphasis on studies that combined basal insulin with oral agents or with short-acting insulins in a basal-bolus approach. The normal physiologic pattern of insulin secretion by pancreatic beta cells consists of a sustained basal insulin level throughout the day, superimposed after meals by relatively large bursts of insulin that slowly decay over 2 to 3 hours (bolus insulin). Basal support with long-acting insulin is a key component of basal-bolus therapy for patients with diabetes who require insulin with or without the addition of oral agents. Newer long-acting agents such as insulin glargine provide a steadier and more reliable level of basal insulin coverage and may have significant advantages over traditional long-acting insulins as part of a basal-bolus treatment strategy

Longitudinal incidence and prevalence of adverse outcomes of diabetes mellitus in elderly patients.

BACKGROUND: The natural history of type 2 diabetes mellitus (DM) in the elderly has not been previously described in a national longitudinal sample. METHODS: This national longitudinal analysis (January 1, 1991, to December 31, 2004) examines mortality and morbidity rates in a representative sample of elderly patients newly diagnosed as having DM. Medicare beneficiaries diagnosed as having DM in 1994 (n=33,772) were compared with a control group (n=25,563) regarding death, lower extremity complications, nephropathy, retinopathy, cardiovascular complications, and cerebrovascular complications. RESULTS: The DM group had excess mortality of 9.2% by year 11 compared with the control group. By 2004, 91.8% of the DM group experienced an adverse complication compared with 72.0% of the control group. The DM group had a higher prevalence and incidence of microvascular and macrovascular complications at all time points compared with controls. Patients with DM were at increased risk for all lower extremity complications, particularly those requiring surgical intervention (gangrene, debridement, and amputation). Cardiovascular complications were a leading cause of morbidity, with 57.6% of the DM group diagnosed as having heart failure compared with 34.1% of the controls. CONCLUSION: Elderly persons newly diagnosed as having DM experienced high rates of complications during 10-year follow-up, far in excess of elderly persons without this diagnosis, implying a substantial burden on the individual and on the health care system

Modification of postprandial hyperglycemia with insulin lispro improves glucose control in patients with type 2 diabetes.

OBJECTIVE: Insulin lispro is a rapid-acting analog of human insulin that can be used to target the postprandial rise in plasma glucose. We designed an open-label randomized crossover study of type 2 diabetic patients with secondary failure of sulfonylurea therapy to determine whether improvement of postprandial hyperglycemia would affect total daily glucose control. RESEARCH DESIGN AND METHODS: Twenty-five type 2 diabetic patients who were poorly controlled on a maximum dose of sulfonylureas were studied in a university hospital clinical research center. In one arm of the study, patients continued therapy with maximum-dose sulfonylureas. In the other arm, patients used a combination therapy with insulin lispro before meals and sulfonylureas. After 4 months, patients were crossed over to the opposite arm. Fasting plasma glucose (FPG) and 1- and 2-h postprandial glucose (after a standardized meal), HbA1c, total, HDL, and LDL cholesterol, and triglyceride levels were measured at the end of each arm of the study. RESULTS: Insulin lispro in combination with sulfonylurea therapy significantly reduced 2-h postprandial glucose concentrations compared with sulfonylureas alone, from 18.6 to 14.2 mmol/l (P &lt; 0.0001), and incremental postprandial glucose area from 617.8 to 472.9 mmol.min.1-1 (P &lt; 0.0007). FPG levels were decreased from 10.9 to 8.5 mmol/l (P &lt; 0.0001), and HbA1c values were reduced form 9.0 to 7.1% (P &lt; 0.0001). Total cholesterol was significantly decreased in the lispro arm from 5.44 to 5.10 mmol/l (P &lt; 0.02). HDL cholesterol concentrations were increased in the lispro arm from 0.88 to 0.96 mmol/l (P &lt; 0.01). The patients weighed significantly more after lispro therapy than after sulfonylureas alone, but the difference was small in absolute terms (sulfonylurea therapy alone, 90.6 kg; lispro therapy, 93.8 kg; P &lt; 0.0001). Two episodes of hypoglycemia (glucose concentrations, &lt; 2.8 mmol/l) were reported by the patients while using lispro. CONCLUSIONS: Previously, it has not been possible to address the effect of treatment of postprandial hyperglycemia specifically. We have now shown that the treatment of postprandial hyperglycemia with insulin lispro markedly improves overall glucose control and some lipid parameters in patients with type 2 diabetes

Diabetes on a cardiovascular ward: adherence to current recommendations.

OBJECTIVES: Improving diabetes and blood pressure control decreases the incidence and progression of microvascular disease. Likewise, screening for microvascular complications is beneficial in the early detection and treatment of these disorders. However, adherence to practice guidelines for screening and treatment in patients with diabetes is suboptimal. This study describes a group of patients with diabetes who were admitted to a cardiology service at an academic medical center. METHODS: Patient interview and chart review were used to determine glycemic control and compliance with practice guidelines. RESULTS: The mean hemoglobin A1c was 8.3%. Only 69% of patients received ophthalmologic examinations, and fewer were screened for nephropathy. Thirty-five percent of patients monitored home blood glucoses less than daily. Nearly 17% had no hemoglobin A1c or lipid checks during the 3 months before admission. CONCLUSIONS: For a group of poorly controlled patients with diabetes who are at high risk for cardiovascular disease, adherence to practice guidelines and the level of diabetes control is inadequate