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

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American Diabetes Association. Diabetes Care. 2015;38(suppl 1):S1-93

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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: mheinsen@ecommunity.com