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Consider this Combo: GLP-1 Receptor Agonists
and Basal Insulin
Matt Heinsen, PharmDPGY2 Pharmacotherapy Resident
Butler University & Community Health Network
This speaker has no actual or potential conflicts of interest to disclose in relation to this presentation
• Discuss the rationale, benefits and literature behind combining glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and basal insulin
• Identify the place in therapy for combination basal insulin and GLP-1RAs
Objectives
An E
mer
ging
Str
ateg
y
American Diabetes Association. Diabetes Care. 2015;38(suppl 1):S1-93
An E
mer
ging
Str
ateg
y
Endocrine practice 2015; 21(S1):1-64
Minimize weight gain
Minimize risk of hypoglycemia
Target treatment to both fasting and postprandial glucose
Eliminate the need for prandial insulin
Reduce insulin requirements
Rationale for Basal Insulin and GLP-1RAs
Trujillo JM and Nuffer W. Pharmacotherapy. 2014;34(11):1174-1186
Buse, et al.
Buse, et al. Ann Intern Med. 2011;154:103-112
StudyDesign
• Randomized, double-blind, placebo-controlled• Primary outcome: change in A1c• Groups: exenatide 10 mcg SQ BID or placebo + insulin
glargine
Results • A1c decreased 1.74% with exenatide and 1.04% in the placebo + insulin group
• Between group difference: -0.69% [CI, -0.93% to -0.46%], p < 0.001
• Weight loss and less insulin required in exenatide group
Applicability • Improved glucose control with addition of GLP-1RA• High incidence of GI AEs with GLP-1RAs
Diamant, et al.
StudyDesign
• Randomized, open-label, noninferiority• Primary outcome: change in A1c• Groups: exenatide 5-10 mcg SQ BID or mealtime insulin
lispro + insulin glargine
Results • Demonstrated noninferiority• Between group difference in A1c was -0.04% [95% CI, -0.18% to 0.11%]• Improved treatment satisfaction in exenatide group,
p < 0.001
Applicability • Support exenatide as a noninsulin addition for patients• Short acting GLP-1RAs may be preferred over bolus
insulin
Diamant, et al. Diabetes Care. 2014;37:2763-2773
Rosenstock, et al.
StudyDesign
• Randomized, open label, noninferiority• Primary outcome: change in A1c• Groups: albiglutide 30 mg SQ weekly (titrated up to
50 mg) or mealtime insulin lispro + insulin glargineResults • Demonstrated noninferiority
• Between group difference in A1c was -0.16% [95% CI, -0.32% to 0.00%], p < 0.001• Hypoglycemia occurred twice as much in the insulin
lispro group
Applicability • Once weekly GLP-1RA use simpler and effective• Study limitations
Rosenstock, et al. Diabetes Care. 2014;37(8):2317-2325
Patient Considerations
Carris, et al. Drugs. 2014;74:2141-2152Trujillo JM and Nuffer W. Pharmacotherapy. 2014;34(11):1174-1186
Need for additional A1c lowering
Desire to avoid prandial insulin
Concern for AEs: weight gain, hypoglycemia
Cost considerations
Initiating GLP-1RA Therapy
Carris, et al. Drugs. 2014;74:2141-2152
Empiric reduction of basal insulin
Dose titration Adverse GI effects
Caution in elderly
Potential renal adjustments
Use of delivery devices
• Combination long acting insulin and GLP-1RA products• Insulin degludec and liraglutide recently
approved in Europe• Insulin glargine and lixisenatide
In the Pipeline . . .
Combination GLP-1 Receptor Agonists and Basal
Insulin
Matt Heinsen, PharmDPGY2 Pharmacotherapy Resident
Butler University & Community Health NetworkEmail: [email protected]