Philip Levin

Combination therapy with insulin glargine and exenatide: real-world outcomes in patients with type 2 diabetes

Abstract Objective: To investigate the real-world use of combination insulin glargine/exenatide therapy for type 2 diabetes mellitus (T2DM) and associated treatment persistence and glycemic control. Methods: In this retrospective study, data were extracted from a national US insurance claims database for patients with T2DM for whom insulin glargine and exenatide were co-prescribed in differing order: insulin glargine added after exenatide (EXE+); exenatide added after insulin glargine (GLA+); glargine and exenatide initiated together (GLA + EXE). Patients had continuous health plan coverage for 6 months pre- (baseline) and 1-year post-index (follow-up). Results: A total of 453 patients were eligible for analysis: 141 patients were included in the EXE+ cohort, 281 in the GLA+ cohort, and 31 in the GLA + EXE cohort. There were significant differences between the groups at baseline, including a significantly lower A1C in the GLA+ versus the EXE+ cohort (p = 0.0023). Around one third of patients stayed on both drugs up until the end of the follow-up period (GLA+: 30.2%; EXE+: 29.0%; GLA + EXE: 29.0%). However, more patients stayed on insulin glargine than on exenatide in each cohort. Significant A1C reductions were observed in each of the cohorts at follow-up: GLA+: −0.4%; EXE+: −0.9%; GLA + EXE: −1.2%; p < 0.01, and were significantly higher in the GLA + EXE and EXE+ cohorts than in the GLA+ cohort (p = 0.03 and p = 0.002, respectively). The mean number of hypoglycemic events increased slightly from baseline but remained low in each of the cohorts (GLA+: 0.12 to 1.42; EXE+: 0.09 to 1.04; GLA + EXE: 0.23 to 1.87 per patient, all p > 0.1). Conclusions: Combined therapy with insulin glargine and exenatide resulted in A1C reductions in T2DM patients with poor glycemic control without a significantly increased risk of hypoglycemia irrespective of treatment order. Limitations of this study are the between-cohort differences at baseline, lack of a comparator group, and small n number, particularly in the GLA + EXE cohort.

Clinical outcomes using long-term combination therapy with insulin glargine and exenatide in patients with type 2 diabetes mellitus

OBJECTIVE To examine the long-term effects of combination insulin glargine/exenatide treatment on glycemic control. METHODS We conducted a 24-month retrospective US chart review of patients with inadequately controlled type 2 diabetes (T2DM) and hemoglobin A1c (A1C) levels >7.0% for whom glargine and exenatide were coprescribed in differing order (glargine added after exenatide [exenatide/glargine]; exenatide added after glargine [glargine/exenatide]). Treatment order groups were combined to form a pooled treatment group. Changes from baseline in A1C, patients with A1C ≤7.0%, body weight, glargine/exenatide daily dose, oral antidiabetic drug (OAD) use, and hypoglycemia were evaluated. RESULTS Treatment groups were similar at baseline; however, patients in the glargine/exenatide group (n = 121) (vs exenatide/glargine group [n = 44]) had longer disease duration (11.8 vs 8.0 years) and took fewer OADs (1.7 vs 2.3). Overall, baseline A1C was 8.8 ± 1.3% and weight was 109.5 ± 25.3 kg. Significant A1C reductions emerged at month 6 and persisted throughout 24 months (vs baseline) in both treatment groups (pooled: -0.7 ± 1.6; P<.001), and 33.0% of patients achieved an A1C level ≤7.0%. After 24 months of exenatide/glargine, body weight remained unchanged (0.7 ± 8.3 kg; P = .640). With glargine/exenatide, body weight decreased (-2.5 ± 6.7 kg; P = .001). At month 24, daily glargine dose was 0.40 ± 0.23 units/kg for the exenatide/glargine group and 0.47 ± 0.30 units/kg for the glargine/exenatide group. Hypoglycemia frequency was similar in both treatment groups. CONCLUSIONS Regardless of treatment order, long-term combined therapy with glargine and exenatide for up to 24 months in patients with inadequately controlled T2DM suggests reduction of A1C without significant weight gain or increased hypoglycemia risk.

Therapeutically interchangeable? A study of real-world outcomes associated with switching basal insulin analogues among US patients with type 2 diabetes mellitus using electronic medical records data

To evaluate real‐world clinical outcomes for switching basal insulin analogues [insulin glargine (GLA) and insulin detemir (DET)] among US patients with type 2 diabetes mellitus (T2DM).

A Real-world Study of Treatment Patterns and Outcomes in US Managed-Care Patients With Type 2 Diabetes Initiating Injectable Therapies

Examine real‐world outcomes in patients with type 2 diabetes mellitus (T2DM) initiating injectable therapy as part of the Initiation of New Injectable Treatment Introduced after Antidiabetic Therapy with Oral‐only Regimens (INITIATOR) study.

Practical combination therapy based on pathophysiology of type 2 diabetes

Type 2 diabetes is a complex, chronic, and progressive condition that often necessitates the use of multiple medications to achieve glycemic goals. Clinical guidelines generally recommend intensifying pharmacotherapy if glycemic goals are not achieved after 3 months of treatment. However, for many patients with type 2 diabetes, treatment intensification is delayed or does not occur. Initiating combination therapy early in the disease course has the potential to delay disease progression and improve patient outcomes. Guidelines generally provide a list of agents that may be used in combination regimens and emphasize individualization of treatment. The purpose of this review is to discuss the rationale for combination therapy, considering treatment effects on pathophysiologic aspects of type 2 diabetes and individual drug profiles. The combination of newer antidiabetes therapies with complementary mechanisms of action provides the opportunity to target multiple sites of tissue, organ, and cellular dysfunction.

Clinical and Economic Outcomes Associated With the Timing of Initiation of Basal Insulin in Patients With Type 2 Diabetes Mellitus Previously Treated With Oral Antidiabetes Drugs

PURPOSE In patients with type 2 diabetes mellitus (T2DM) not achieving glycemic targets using oral antidiabetes drugs (OADs), studies suggest that timely insulin initiation has clinical benefits. Insulin initiation at the early versus late stage of disease progression has not been explored in detail. This retrospective database analysis investigated clinical and economic outcomes associated with the timing of insulin initiation in patients with T2DM treated with ≥1 OAD in a real-world US setting. METHODS This study linked data from the Truven Health MarketScan(®) Commercial database, Medicare Supplemental database, and Quintiles Electronic Medical Records database. A total of 1830 patients with T2DM were included. Patients were grouped according to their OAD use before basal insulin initiation (1, 2, or ≥3 OADs) as a proxy for the timing of insulin initiation. Clinical and economic outcomes were evaluated over 1 year of follow-up. FINDINGS During follow-up the 1 OAD group, compared with the 2 and ≥3 OADs groups, had a greater reduction in glycosylated hemoglobin A1c (-1.7% vs -1.0% vs -0.9%, respectively; P < 0.0001), greater achievement of glycemic target (38.2% vs 26.7% vs 19.6%, respectively; P < 0.0001), and a lower incidence of hypoglycemia (2.7% vs 6.6% vs 5.0%, respectively; P = 0.0002), with no difference in total health care costs (

Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research.

21,167 vs

COMPARING CLINICAL OUTCOMES AND COSTS FOR DIFFERENT TREATMENT INTENSIFICATION APPROACHES IN PATIENTS WITH TYPE 2 DIABETES UNCONTROLLED ON BASAL INSULIN: ADDING GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONISTS VERSUS ADDING RAPID-ACTING INSULIN OR INCREASING BASAL INSULIN DOSE

21,060 vs

PREDICTORS AND CLINICAL OUTCOMES OF TREATMENT INTENSIFICATION IN PATIENTS WITH TYPE 2 DIABETES UNCONTROLLED ON BASAL INSULIN IN A REAL-WORLD SETTING

20,133, respectively). IMPLICATIONS This study shows that early insulin initiation (represented by the 1 OAD group) may be clinically beneficial to patients with T2DM not controlled with OADs, without adding to costs. This supports the call for timely initiation of individualized insulin therapy in this population.

Real-world clinical responses in patients with type 2 diabetes mellitus adding exenatide BID (EBID) or mealtime insulin to basal insulin: a retrospective study using electronic medical record data

Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) act by increasing insulin secretion, decreasing glucagon secretion, slowing gastric emptying, and increasing satiety. Objective Published evidence directly comparing GLP-1RAs with other approved treatments for type 2 diabetes (T2D) was systematically reviewed. Methods A literature search was performed using MEDLINE and Embase databases to identify papers comparing GLP-1RAs with other classes of glucose-lowering therapy in patients with T2D. Results Of the 1303 papers identified, 57 met the prespecified criteria for a high-quality clinical trial or retrospective study. The efficacy and tolerability of approved GLP-1RAs (exenatide twice daily or once weekly, dulaglutide, liraglutide, lixisenatide, and albiglutide) were compared with insulin products (23 prospective studies + seven retrospective studies), dipeptidyl peptidase-4 inhibitors (11 prospective studies + three retrospective studies), sulfonylureas (nine prospective studies + one retrospective study), thiazolidinediones (five prospective studies), and metformin (two prospective studies). GLP-1RAs are effective as a second-line therapy in improving glycemic parameters in patients with T2D. Reductions in glycated hemoglobin from baseline with GLP-1RAs tended to be greater or similar compared with insulin therapy. GLP-1RAs were consistently more effective in reducing body weight than most oral glucose-lowering drugs and insulin and were associated with lower hypoglycemia risk versus insulin or sulfonylureas. GLP-1RAs improved cardiovascular risk factors, and preliminary data suggest they improve cardiovascular outcomes in patients with T2D compared with oral glucose-lowering drugs. However, results from ongoing studies are awaited to confirm these early findings. Conclusion This systematic review found that GLP-1RAs are an effective class of glucose-lowering drugs for T2D.