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CME

Insulin Glargine Noninferior to Insulin Lispro in Patients With Type 2 Diabetes

  • Authors: News Author: Laurie Barclay, MD
    CME Author: Laurie Barclay, MD
  • CME Released: 3/31/2008
  • THIS ACTIVITY HAS EXPIRED
  • Valid for credit through: 3/31/2009
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Target Audience and Goal Statement

This article is intended for primary care clinicians, endocrinologists, diabetologists, and other specialists who care for patients with type 2 diabetes.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  1. Compare glycemic control with insulin glargine given once daily vs insulin lispro given 3 times daily in patients with type 2 diabetes mellitus inadequately controlled by oral hypoglycemic agents.
  2. Compare hypoglycemic events and other effects of insulin glargine given once daily vs insulin lispro given 3 times daily in patients with type 2 diabetes mellitus inadequately controlled by oral hypoglycemic agents.


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Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.


Author(s)

  • Laurie Barclay, MD

    Laurie Barclay, MD, is a freelance reviewer and writer for Medscape.

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Editor(s)

  • Brande Nicole Martin

    Brande Nicole Martin is the News CME editor for Medscape Medical News.

    Disclosures

    Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

CME Author(s)

  • Laurie Barclay, MD

    Freelance reviewer and writer for Medscape

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.


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CME

Insulin Glargine Noninferior to Insulin Lispro in Patients With Type 2 Diabetes

Authors: News Author: Laurie Barclay, MD CME Author: Laurie Barclay, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

CME Released: 3/31/2008

Valid for credit through: 3/31/2009

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March 31, 2008 — In patients with type 2 diabetes mellitus whose disease is not controlled by oral hypoglycemic agents, treatment with insulin glargine once daily was noninferior to insulin lispro 3 times daily in reducing hemoglobin A1c levels, according to the results of a 44-week, parallel, open study reported in the March 29 issue of The Lancet.

"As type 2 diabetes mellitus progresses, oral hypoglycaemic agents often fail to maintain blood glucose control and insulin is needed, write Reinhard G Bretzel, MD, from Medizinische Klinik und Poliklinik III, Justus-Liebig-Universität, Giessen, Germany, and colleagues from the APOLLO study (A Parallel design comparing an Oral antidiabetic drug combination therapy with either Lantus once daily or Lispro at mealtime in type 2 diabetes patients failing Oral treatment). "We investigated whether the addition of once-daily insulin glargine is non-inferior to three-times daily prandial insulin lispro in overall glycaemic control in adults with inadequately controlled type 2 diabetes mellitus taking oral hypoglycaemic agents."

At 69 study sites across Europe and Australia, 418 patients with type 2 diabetes mellitus inadequately controlled by oral hypoglycemic agents were randomized to receive either insulin glargine taken once daily at the same time every day or insulin lispro 3 times per day. The goal of this study was to compare the 2 regimens in the change in hemoglobin A1c levels from baseline to endpoint (week 44). Randomization was accomplished with a central randomization service, and analysis was per protocol.

There were 205 patients randomized to receive insulin glargine and 210 to receive insulin lispro. In the insulin glargine group, mean decrease in hemoglobin A1c levels was –1.7% (from 8.7% ± 1.0% to 7.0% ± 0.7%) vs –1.9% in the insulin lispro group (from 8.7% ± 1.0% to 6.8% ± 0.9%). This was within the predefined limit for noninferiority of 0.4% (difference = 0.157; 95% confidence interval [CI], –0.008 to 0.322).

In the insulin glargine group, 106 (57%) patients reached hemoglobin A1c levels of 7% or less vs 131 (69%) in the insulin lispro group. Compared with the insulin lispro group, the glargine group fared better in decreased mean fasting blood glucose levels (–4.3 ± 2.3 mmol/L vs –1.8 ± 2.3 mmol/L; P < .0001) and nocturnal blood glucose levels (–3.3 ± 2.8 mmol/L vs –2.6 ± 2.9 mmol/L; P = .0041). However, insulin lispro was associated with better control of postprandial blood glucose levels throughout the day (P < .0001).

Insulin glargine was associated with lower incidence of hypoglycemic events vs lispro (5.2; 95% CI, 1·9 - 8·9 vs 24.0; 95% CI, 21 - 28, events per patient per year; P < .0001). Mean weight gains were 3.01 ± 4.33 kg with insulin glargine and 3.54 ± 4.48 kg with insulin lispro. Compared with insulin lispro, insulin glargine was associated with greater improvement of treatment satisfaction (mean difference, 3.13; 95% CI, 2.04 - 4.22).

"A therapeutic regimen involving the addition of either basal or prandial insulin analogue is equally effective in lowering haemoglobin A1c," the study authors write. "We conclude that insulin glargine provides a simple and effective option that is more satisfactory to patients than is lispro for early initiation of insulin therapy, since it was associated with a lower risk of hypoglycaemia, fewer injections, less blood glucose self monitoring, and greater patient satisfaction than was insulin lispro. . . . Evidence from the APOLLO study suggests that the addition of insulin glargine to therapies with oral hypoglycaemic agents can be regarded as a first-line insulin initiation approach in type 2 diabetes mellitus, as has been recommended in a joint consensus guideline by the American Diabetes Association and European Association for the Study of Diabetes."

This study was funded by sanofi-aventis, which employs one of the study authors. Some of the study authors have disclosed various financial relationships with Bayer, Develogen, GlaxoSmithKline, Lilly, MSD, Novo Nordisk, sanofi-aventis, Pfizer, Roche, Novartis, and Health Psychology Research.

In an accompanying editorial, Yogish C. Kudva, MD, and Victor M. Montori, MD, from the Mayo Clinic in Rochester, Minnesota, discuss various other therapeutic options for patients with type 2 diabetes.

"APOLLO suggests that insulin glargine should be considered after metformin and sulphonylureas fail; patients might consider this approach consistent with their preferences or may want to try exenatide, an injectable drug that might help with weight loss," Drs. Kudva and Montori write. "The availability of these options will differ across health-care systems with some limiting patients' access to the different agents or forcing a particular treatment algorithm that limits access to expensive treatments. Whether this algorithm is sensitive to patients' preferences and whether patients' participation in the choice of drugs can affect adherence to therapy remains unclear."

Dr. Kudva has disclosed receiving funding for a research trial from sanofi-aventis. Dr. Montori has disclosed no relevant financial relationships.

Lancet. 2008;371:1047-1048, 1073-1084.

Clinical Context

Achieving tight glycemic control is a desired, but difficult, goal in patients with type 2 diabetes. Secondary failure (hemoglobin A1c > 7%) develops in approximately half of patients after a few years of treatment with oral hypoglycemic agents, and supplementary insulin therapy is needed to achieve and maintain good glycemic control. The risk for hypoglycemia and need for frequent injections hinder compliance with insulin treatment.

The basal insulin analogue glargine has a long duration of action (approximately 24 hours), with little or no peak in blood insulin concentration and glycemic control equivalent to NPH insulin but with a lower rate of hypoglycemia. The short-acting insulin analogue lispro, given 3 times daily with meals, also compares favorably with NPH insulin in glycemic control and rates of hypoglycemia. The optimal regimen is still undetermined.

Study Highlights

  • The goal of the APOLLO study was to determine whether adding once-daily insulin glargine targeting fasting blood glucose levels is noninferior to 3-times-daily prandial insulin lispro targeting postprandial blood glucose levels in overall glycemic control in adults with type 2 diabetes inadequately controlled by oral hypoglycemic agents.
  • At 69 study sites across Europe and Australia, 418 patients with type 2 diabetes inadequately controlled by oral hypoglycemic agents were randomized to receive either insulin glargine taken once daily at the same time every day or insulin lispro 3 times per day.
  • Inclusion criteria were ages 18 to 75 years, type 2 diabetes mellitus for 1 year or more with hemoglobin A1c concentrations of 7.5% to 10.5%, use of oral hypoglycemic agents (excluding alpha-glucosidase inhibitors) for 6 months or more with stable doses for 3 months or more before study entry, fasting blood glucose concentrations of 6.7 mmol/L or more, BMI of 35 kg/m2 or less, and willingness to self-monitor blood glucose levels.
  • The 2 regimens were compared in the change in hemoglobin A1c from baseline to endpoint (week 44).
  • A central randomization service was used, and analysis was per protocol.
  • 205 patients were randomized to receive insulin glargine and 210 to receive insulin lispro.
  • Mean decrease in hemoglobin A1c levels was –1.7% in the insulin glargine group (from 8.7% ± 1.0% to 7.0% ± 0.7%) vs –1.9% in the insulin lispro group (from 8.7% ± 1.0% to 6.8% ± 0.9%).
  • This difference of 0.157 (95% CI, –0.008 to 0.322) was within the predefined limit for noninferiority of 0.4%.
  • In the insulin glargine group, 106 (57%) patients reached hemoglobin A1c levels of 7% or less vs 131 (69%) in the insulin lispro group.
  • The glargine group fared better than the insulin lispro group in decreased mean fasting blood glucose levels (–4.3 ± 2.3 mmol/L vs –1.8 ± 2.3 mmol/L; P < .0001) and nocturnal blood glucose levels (–3.3 ± 2.8 mmol/L vs –2.6 ± 2.9 mmol/L; P = .0041).
  • Compared with insulin glargine, insulin lispro was associated with better control of postprandial blood glucose levels throughout the day (P < .0001).
  • Targeting fasting blood glucose or postprandial blood glucose levels were both equally effective in improving hemoglobin A1c levels.
  • There were no differences in adherence to titration targets when maximum (baseline) or minimum (endpoint) hemoglobin A1c concentrations were compared for insulin glargine and insulin lispro treatment.
  • There were fewer hypoglycemic events per patient per year with insulin glargine vs lispro (5.2; 95% CI, 1·9 - 8·9 vs 24.0; 95% CI, 21 - 28; P < .0001).
  • Mean weight gains were 3.01 ± 4.33 kg with insulin glargine and 3.54 ± 4.48 kg with insulin lispro.
  • Insulin glargine was associated with greater improvement of treatment satisfaction vs insulin lispro (mean difference, 3.13; 95% CI, 2.04 - 4.22).
  • Based on these findings, the investigators concluded that insulin glargine provides a simple and effective option that is more satisfactory to patients vs lispro for early initiation of insulin therapy because it was associated with a lower risk for hypoglycemia, fewer injections, less self-monitoring of blood glucose levels, and greater patient satisfaction.
  • These findings also suggest that adding insulin glargine to treatments with oral hypoglycemic agents can be regarded as a first-line approach to starting insulin in type 2 diabetes mellitus, as recommended in a joint consensus guideline by the American Diabetes Association and European Association for the Study of Diabetes.

Pearls for Practice

  • In the APOLLO study of patients with type 2 diabetes mellitus whose disease was not controlled by oral hypoglycemic agents, treatment with insulin glargine once daily was noninferior to insulin lispro 3 times daily in reducing hemoglobin A1c concentrations.
  • Findings of the APOLLO study suggest that insulin glargine offers a simple and effective option that is more satisfactory to patients vs lispro for early initiation of insulin therapy because it is associated with a lower risk for hypoglycemia, fewer injections, less self-monitoring of blood glucose levels, and greater patient satisfaction.

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