Advancing basal insulin replacement in type 2 diabetes inadequately controlled with insulin glargine plus oral agents: a comparison of adding albiglutide, a weekly GLP-1 receptor agonist, versus thrice-daily prandial insulin lispro. []
Advancing basal insulin replacement in type 2 diabetes inadequately controlled with insulin glargine plus oral agents: a comparison of adding albiglutide, a weekly GLP-1 receptor agonist, versus thrice-daily prandial insulin lispro. []
- 2014
Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1999 - 2006
CONCLUSIONS: Weekly albiglutide is a simpler therapeutic option than thrice-daily lispro for advancing basal insulin glargine therapy, resulting in comparable HbA1c reduction with weight loss and lower hypoglycemia risk.Copyright � 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. OBJECTIVE: GLP-1 receptor agonists may provide an alternative to prandial insulin for advancing basal insulin therapy. Harmony 6 was a randomized, open-label, active-controlled trial testing once-weekly albiglutide vs. thrice-daily prandial insulin lispro as an add-on to titrated once-daily insulin glargine. RESEARCH DESIGN AND METHODS: Patients taking basal insulin (with or without oral agents) with HbA1c 7-10.5% (53-91 mmol/mol) entered a glargine standardization period, followed by randomization to albiglutide, 30 mg weekly (n = 282), subsequently uptitrated to 50 mg, if necessary, or thrice-daily prandial lispro (n = 281) while continuing metformin and/or pioglitazone. Glargine was titrated to fasting plasma glucose of <5.6 mmol/L, and lispro was adjusted based on glucose monitoring. The primary end point was the difference in the HbA1c change from baseline at week 26. RESULTS: At week 26, HbA1c decreased from baseline by -0.82 +/- SE 0.06% (9.0 mmol/mol) with albiglutide and -0.66 +/- 0.06% (7.2 mmol/mol) with lispro; treatment difference, -0.16% (95% CI -0.32 to 0.00; 1.8 mmol/mol; P < 0.0001), meeting the noninferiority end point (margin, 0.4%). Weight decreased with albiglutide but increased with lispro (-0.73 +/- 0.19 kg vs. +0.81 +/- 0.19 kg). The mean glargine dose increased from 47 to 53 IU (albiglutide) and from 44 to 51 IU (lispro). Adverse events for albiglutide versus lispro included severe hypoglycemia (0 vs. 2 events), documented symptomatic hypoglycemia (15.8% vs. 29.9%), nausea (11.2% vs. 1.4%), vomiting (6.7% vs. 1.4%), and injection site reactions (9.5% vs. 5.3%).
0149-5992
*Diabetes Mellitus, Type 2/dt [Drug Therapy]
*Glucagon-Like Peptide 1/aa [Analogs & Derivatives]
*Hypoglycemic Agents/ad [Administration & Dosage]
*Insulin Lispro/ad [Administration & Dosage]
*Insulin, Long-Acting/ad [Administration & Dosage]
*Insulin/ad [Administration & Dosage]
Administration, Oral
Adult
Aged
Blood Glucose/de [Drug Effects]
Diabetes Mellitus, Type 2/me [Metabolism]
Drug Administration Schedule
Drug Substitution
Drug Therapy, Combination
Female
Glucagon-Like Peptide 1/ad [Administration & Dosage]
Hemoglobin A, Glycosylated/an [Analysis]
Humans
Male
Meals
Metformin/ad [Administration & Dosage]
Middle Aged
Receptors, Glucagon/ag [Agonists]
Thiazolidinediones/ad [Administration & Dosage]
Treatment Outcome
MedStar Health Research Institute
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1999 - 2006
CONCLUSIONS: Weekly albiglutide is a simpler therapeutic option than thrice-daily lispro for advancing basal insulin glargine therapy, resulting in comparable HbA1c reduction with weight loss and lower hypoglycemia risk.Copyright � 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. OBJECTIVE: GLP-1 receptor agonists may provide an alternative to prandial insulin for advancing basal insulin therapy. Harmony 6 was a randomized, open-label, active-controlled trial testing once-weekly albiglutide vs. thrice-daily prandial insulin lispro as an add-on to titrated once-daily insulin glargine. RESEARCH DESIGN AND METHODS: Patients taking basal insulin (with or without oral agents) with HbA1c 7-10.5% (53-91 mmol/mol) entered a glargine standardization period, followed by randomization to albiglutide, 30 mg weekly (n = 282), subsequently uptitrated to 50 mg, if necessary, or thrice-daily prandial lispro (n = 281) while continuing metformin and/or pioglitazone. Glargine was titrated to fasting plasma glucose of <5.6 mmol/L, and lispro was adjusted based on glucose monitoring. The primary end point was the difference in the HbA1c change from baseline at week 26. RESULTS: At week 26, HbA1c decreased from baseline by -0.82 +/- SE 0.06% (9.0 mmol/mol) with albiglutide and -0.66 +/- 0.06% (7.2 mmol/mol) with lispro; treatment difference, -0.16% (95% CI -0.32 to 0.00; 1.8 mmol/mol; P < 0.0001), meeting the noninferiority end point (margin, 0.4%). Weight decreased with albiglutide but increased with lispro (-0.73 +/- 0.19 kg vs. +0.81 +/- 0.19 kg). The mean glargine dose increased from 47 to 53 IU (albiglutide) and from 44 to 51 IU (lispro). Adverse events for albiglutide versus lispro included severe hypoglycemia (0 vs. 2 events), documented symptomatic hypoglycemia (15.8% vs. 29.9%), nausea (11.2% vs. 1.4%), vomiting (6.7% vs. 1.4%), and injection site reactions (9.5% vs. 5.3%).
0149-5992
*Diabetes Mellitus, Type 2/dt [Drug Therapy]
*Glucagon-Like Peptide 1/aa [Analogs & Derivatives]
*Hypoglycemic Agents/ad [Administration & Dosage]
*Insulin Lispro/ad [Administration & Dosage]
*Insulin, Long-Acting/ad [Administration & Dosage]
*Insulin/ad [Administration & Dosage]
Administration, Oral
Adult
Aged
Blood Glucose/de [Drug Effects]
Diabetes Mellitus, Type 2/me [Metabolism]
Drug Administration Schedule
Drug Substitution
Drug Therapy, Combination
Female
Glucagon-Like Peptide 1/ad [Administration & Dosage]
Hemoglobin A, Glycosylated/an [Analysis]
Humans
Male
Meals
Metformin/ad [Administration & Dosage]
Middle Aged
Receptors, Glucagon/ag [Agonists]
Thiazolidinediones/ad [Administration & Dosage]
Treatment Outcome
MedStar Health Research Institute
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't