Thomas Seck

Efficacy and safety of treatment with sitagliptin or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy: a randomized, double-blind, non-inferiority trial

Aim: To evaluate the efficacy and safety of adding sitagliptin or glimepiride to the treatment regimen of patients with type 2 diabetes mellitus and inadequate glycaemic control on metformin monotherapy.

A treatment strategy implementing combination therapy with sitagliptin and metformin results in superior glycaemic control versus metformin monotherapy due to a low rate of addition of antihyperglycaemic agents

Aims: Combination therapy with sitagliptin and metformin has shown superior efficacy compared with metformin monotherapy. In this study, we compare two strategies: initial combination therapy with sitagliptin/metformin as a fixed‐dose combination (FDC) and initial metformin monotherapy, with the option to add additional antihyperglycaemic agents (AHAs) in either treatment arm during the second phase of the study in order to reach adequate glycaemic control.

Efficacy and safety of sitagliptin and the fixed-dose combination of sitagliptin and metformin vs. pioglitazone in drug-naïve patients with type 2 diabetes

Aim:  The efficacy and safety of sitagliptin (SITA) monotherapy and SITA/metformin (MET) vs. pioglitazone (PIO) were assessed in patients with type 2 diabetes and moderate‐to‐severe hyperglycaemia (A1C = 7.5–12.0%).

Sitagliptin more effectively achieves a composite endpoint for A1C reduction, lack of hypoglycemia and no body weight gain compared with glipizide

Sitagliptin and glipizide added to metformin provided similar degrees of glycemic efficacy in patients with type 2 diabetes with inadequate glycemic control on metformin monotherapy at 1 year; however, significantly more patients in the sitagliptin group achieved an A1C reduction of >0.5% without hypoglycemia and without an increase in body weight.

Underutilization of statins in patients with type 2 diabetes in US clinical practice: a retrospective cohort study

Abstract Objectives: To estimate the proportion of patients with type 2 diabetes who were eligible for statin treatment per American Diabetes Association (ADA) recommendations and the proportion who were actually prescribed a statin in US clinical practice. Factors associated with receiving a statin prescription were also determined. Methods: Patients ≥25 years diagnosed with type 2 diabetes or had received prescriptions for antihyperglycemic agents between 7/2006 and 6/2008 were identified within a large electronic medical record database. Eligibility for statin therapy was determined according to 2008 ADA recommendations. Statin use was assessed based on prescription records during a 12-month follow-up period. An adjusted logistic regression analysis was performed to estimate the likelihood of statin use in relation to selected baseline characteristics. Results: Of the 125,464 patients identified, 98.5% were eligible for statin therapy. Only 62.9% received a statin prescription during follow-up period. In an adjusted logistic regression, factors associated with increased likelihood of statin use were older age, male gender, smoking, history of cardiovascular conditions, and receiving an antihyperglycemic, antihypertensive, or anticoagulant prescription at baseline (all p < 0.05). Limitations: Of the patients who did not receive statin during follow-up, 13% of them were previously on a statin during the baseline period. The reasons for discontinuing therapy are not known. It cannot be excluded that some of these patients were intolerant or had contraindications to statin. The data on prescription dispensing and compliance were not recorded. Conclusions: Nearly all patients with type 2 diabetes were eligible for statin therapy, but less than two-thirds received statin therapy in US clinical practice. Efforts to minimize this gap are warranted.

Lower risk of hypoglycemia with sitagliptin compared to glipizide when either is added to metformin therapy: a pre-specified analysis adjusting for the most recently measured HbA1c value

Abstract Background: In a previously-published study, adding sitagliptin or glipizide to ongoing metformin therapy provided similar HbA1c improvement (both groups, −0.7%) after 52 weeks in patients with type 2 diabetes (T2DM). Significantly fewer patients experienced symptomatic hypoglycemia with sitagliptin (5% of 588 patients) compared to glipizide (32% of 584 patients). Glycemic efficacy and patient characteristics may influence hypoglycemic events. The present analysis evaluated the risk of hypoglycemia with sitagliptin or glipizide after adjusting for the most recently measured HbA1c value. Methods: Data for this analysis were from the aforementioned 52-week, randomized, double-blind, active-controlled study. The primary endpoint was confirmed hypoglycemia (i.e., symptomatic hypoglycemia confirmed with a concurrent fingerstick glucose ≤70 mg/dL [3.9 mmol/L]); the secondary endpoint was severe hypoglycemia (requiring medical or non-medical assistance or symptoms of neuroglycopenia). Complementary log-log regression random effects models with terms for treatment, most recently measured HbA1c value, time (i.e., days since randomization), gender, and age (< or ≥65 years) were used to assess adjusted subject-specific treatment effects. Results: Over the full range of HbA1c levels and follow-up time, the risk of confirmed hypoglycemic events was lower with sitagliptin compared with glipizide (31 vs. 448 events; adjusted hazard ratio [HR] = 0.05 [95% CI: 0.03, 0.09], p < 0.001). The risk was also lower with sitagliptin in the younger (HR = 0.06 [95% CI: 0.03, 0.12], p < 0.001) and older (HR = 0.02 [0.01, 0.08], p < 0.001) age groups compared with glipizide. For severe hypoglycemia events (2 vs. 22), the risk was lower with sitagliptin (HR = 0.08 [95% CI: 0.01, 0.47]; p = 0.005). Limitations: The actual time between the HbA1c measurement and the hypoglycemic event was variable and not controlled for in the analysis. Conclusion: In pre-specified analyses adjusting for the most recently measured HbA1c value, there was a substantial reduction in risk for confirmed hypoglycemia with sitagliptin compared to glipizide when added to ongoing metformin therapy in patients with T2DM. The risk of confirmed hypoglycemia was very low in younger and older patients treated with sitagliptin.

Assessment of AACE/ACE recommendations for initial dual antihyperglycemic therapy using the fixed-dose combination of sitagliptin and metformin versus metformin.

OBJECTIVE The American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) diabetes algorithm recommends a stratified approach to initial therapy to achieve a glycated hemoglobin (HbA1c) goal of ≤6.5% in patients with type 2 diabetes mellitus (T2DM) who have inadequate glycemic control. Data from a double-blind study in drug-naïve T2DM patients comparing initial monotherapy with metformin (MET) with initial dual therapy with a fixed-dose combination of sitagliptin and MET (SITA/MET FDC) was used to determine AACE/ACE HbA1c goal attainment in these treatment groups. METHODS A total of 1,250 patients (mean baseline HbA1c = 9.9%) were randomized 1:1 to SITA/MET FDC 50/500 mg twice daily (b.i.d.) or MET 500 mg b.i.d. for 18 weeks. SITA/MET FDC and MET were uptitrated over 4 weeks to 50/1,000 mg b.i.d. and 1,000 mg b.i.d., respectively. RESULTS At week 18, a higher percentage of patients receiving SITA/MET FDC had HbA1c levels ≤6.5% and <7% than those receiving MET alone within each of the 3 AACE/ACE HbA1c categories (6.5-7.5%, >7.5-9.0%, and >9.0%). Of patients with a baseline HbA1c >7.5-9.0% who initiated SITA/MET FDC, 48.6% achieved an HbA1c ≤6.5% at week 18 compared with 23.1% of patients who initiated MET monotherapy (P<.001). In patients with a baseline HbA1c >9.0%, 24.0% on SITA/MET FDC achieved an HbA1c ≤6.5% compared with 12.8% on MET alone (P<.001). CONCLUSION In T2DM patients with a baseline HbA1c >7.5-9.0%, substantially more achieved the HbA1c goal of ≤6.5% with initial dual therapy (SITA/MET FDC) than with initial monotherapy (MET), which is in agreement with the AACE/ACE diabetes algorithm.

Time to initiation of oral antihyperglycemic and statin therapy in previously untreated patients with type 2 diabetes in the United States

Abstract Objective: To assess the time from the first observed diagnosis of type 2 diabetes (T2DM) to initiation of an oral antihyperglycemic agent (OAHA) and statin. Methods: In a retrospective US cohort study using the GE electronic medical record database, patients ≥18 years were included if they had a T2DM diagnosis between January 1, 2004 and December 31, 2005 (index period), had a last pre-index HbA1c value ≥7%, and had not received antihyperglycemic agents within one year prior to diagnosis (index date). Patients were eligible for statin therapy but not on a statin within one year before the index date. Patients had medical records for one year prior to (baseline) and two years after (follow up) diagnosis. Results: Of the 2254 eligible patients, 58% were male, mean age was 58 years, mean HbA1c was 8.5%, and mean LDL cholesterol was 115 mg/dL (2.97 mmol/L) at baseline. Additionally, 21% of patients had pre-existing overt cardiovascular disease, 40% had dyslipidemia, 37% were obese, and 11% were smokers. During follow-up, 66.1% and 41.9% of patients initiated an OAHA and a statin, respectively. Among the treated patients, median time from the first observed diabetes diagnosis to therapy initiation was 3 months (interquartile range: 1, 9) for OAHAs and 6 months (2, 13) for statins. Limitations: Treatment initiation with injectable antihyperglycemic agents and/or non-statin lipid-modifying therapies as well as contraindications to OAHAs or statins were not assessed, therefore their impact on our study results cannot be determined. Laboratory measurements were not available for every patient and thus many patients were excluded from the analysis. Conclusion: Treatment initiation with OAHAs and/or statins was suboptimal in patients with T2DM who were treatment eligible and previously untreated with OAHAs and statins. Of those treated, patients initiated treatment with an OAHA more often and earlier than with a statin.

2.3 Cardiovascular (CV) Safety of Linagliptin in Patients with Type 2 Diabetes (T2D): A Pooled Comprehensive Analysis of Prospectively Adjudicated CV Events in Phase 3 Studies (376-OR)

SamenvattingIncidence of CV events is increased in T2D, but the potential for CV risk modulation with glucose lowering therapies is debated. We compared the incidence of CV events and CV mortality in patients with T2D treated with linagliptin (lina), a once daily DPP-4 inhibitor, with non-lina comparators (comp) in 19 double-blind RCTs (duration ≥ 12 weeks).