A Retrospective Evaluation of Glycemic Effects in Veterans With Type - - PowerPoint PPT Presentation

A Retrospective Evaluation of Glycemic Effects in Veterans With Type 2 Diabetes After Addition of SGLT2 Inhibitors or GLP-1 Receptor Agonists to Basal-Bolus Insulin Regimens

Lauren Wilde, PharmD, PGY-2 Ambulatory Care Resident Kansas City VA Medical Center

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Conflict of Interest

• The speaker has no actual or potential conflicts of

interest in relation to this presentation

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Learning Objective

• Evaluate the effects on glycemic control, in addition to

pleiotropic effects and insulin dose requirements, when either an SGLT2 Inhibitor or GLP-1 Receptor Agonist is added to basal-bolus insulin regimens in a Veteran population with Type 2 Diabetes

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Abbreviations

• ADA – American Diabetes Association
• ASCVD – atherosclerotic cardiovascular disease
• DM – Diabetes Mellitus
• eGFR – estimated glomerular function
• GLP-1 – glucagon like peptide 1
• IRB – Institutional Review Board
• SGLT2 – sodium glucose co-transporter 2
• TDD – total daily dose
• VISN – Veterans Integrated Service Networks

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Background1

• An estimated 30.3 million people were affected or

diagnosed with Type 2 DM in the United States in 2015

– More than half are adults aged 45 to 65 years of age

• With an increased prevalence of DM, pharmacological

therapies have continued to expand

– SGLT2 Inhibitors – GLP-1 Receptor Agonists

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SGLT2 Inhibitors2,3

• Mechanism: excretion of glucose through urine

– Minimal to no risk of beta-cell burnout and

• verstimulation
• Place in therapy:

– Second, third, and fourth-line agents – Consider sooner in therapy with established ASCVD

• r if heart failure or chronic kidney disease

predominates – Consider to minimize hypoglycemia or weight gain

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GLP-1 Receptor Agonist2,4

• Mechanism: mimics natural hormone GLP-1:

– Increased insulin secretion – Decreased glucagon release – Decreased hepatic glucose output

• Place in therapy:

– Second, third, and fourth-line agents – Consider sooner in therapy with established ASCVD

• r if heart failure or chronic kidney disease

predominates and unable to utilize SGLT2 inhibitor – Consider to minimize hypoglycemia or weight gain

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VA Population and DM Management

• SGLT2 inhibitors and GLP-1 receptor agonists

relatively restricted

– Due to cost of therapy

• Use of either agent requires prior approval

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Utility of Novel Agents with Insulin3,4

• Studies have shown improvement in A1c and reduction

in insulin doses with combination of either SGLT2 inhibitors or GLP-1 agonists to basal insulin therapy

• Limited evidence evaluating glycemic outcomes when

either agent is added to basal-bolus insulin regimens

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Research Outcomes

Primary Outcome

• Change in A1c from baseline to 12 months after the

addition of either an SGLT2 inhibitor or GLP-1 receptor agonist to basal-bolus insulin regimens

9

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Research Outcomes

Secondary Outcomes

• After the addition of either a SGLT2 inhibitor or GLP-1

receptor agonist to basal-bolus insulin:

• The mean change from baseline to 6, 18, and 24 months in A1c
• The mean change from baseline to 6, 12, 18, and 24 months in:
• Weight
• TDD of basal insulin
• TDD of bolus insulin
• Blood Pressure
• Renal Function
• Safety Outcomes

10

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Methods: Study Design

• Retrospective, multi-center

cohort study

• Flipped PGY2 Research

Project

• Data collected from VA

VISN 15

• Approved through Kansas

City Veteran’s Affairs IRB

– Submitted November 2018 Approved January 2019

https://www.va.gov/directory/guide/map.asp?dnum=1

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Methods: Criteria

• Inclusion Criteria

– US adult Veterans with Type 2 Diabetes – Initiation of either an SGLT2 inhibitor or GLP-1 receptor agonist in addition to a basal-bolus insulin regimen within the defined study period

• January 1st, 2015 to January 1st, 2019

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Methods: Criteria

• Exclusion Criteria

– Type 1 Diabetes – Acute Metabolic Complications present at the time of study drug initiation – Initiation of an SGLT2 inhibitor within 12 months of GLP-1 receptor initiation, or vice versa – If A1c was missing at 6 and 12 months following study drug initiation – If the study agent was discontinued within 12 months of initiation – If there was no active prescription for the study agent at 6, 12, and 18 months – eGFR less than 45 ml/min/1.73m2 at study drug initiation

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Results: Patient Population

Patients Meeting Inclusion Criteria (n = 677) GLP-1 Receptor Agonist Initiation (n = 403) Excluded (n = 193) Included (n = 210) SGLT2 Inhibitor Initiation (n = 274) Excluded (n = 176) Included (n = 98)

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Results: Patient Demographics

SGLT2 Inhibitor (N = 98) GLP-1 Receptor Agonist (N = 210) Age, years, mean 64.8 62.3 Male Sex, no. (%) 95 (96.9) 199 (94.8) A1c, %, mean 8.73 8.94 Weight, pounds, mean 263.3 268.5 ASCVD History, No. (%) 34 (35) 59 (28) TDD of Basal Insulin, units, mean 82 85 TDD of Bolus Insulin, units, mean 85 78 Blood Pressure, mmHg, mean 133/72 132/74 eGFR, ml/min/1.73m2, mean 73 66 Primary Study Agent (%) empagliflozin (98) liraglutide (88)

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Results: Primary Outcome

• 1.2
• 1
• 0.8
• 0.6
• 0.4
• 0.2

Baseline 6 months 12 months

Mean Change in A1c (%)

Mean Change in A1c

SGLT2 Inhibitor GLP-1 Receptor Agonist

• 0.59 ± 1.83%
• 0.91% ± 1.91%

Baseline 6 months 12 months SGLT2 Inhibitor (n) 98 88 98 GLP-1 Receptor Agonist (n) 210 203 210

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Results: Secondary Outcomes

• 1.6
• 1.4
• 1.2
• 1
• 0.8
• 0.6
• 0.4
• 0.2

Baseline 6 months 12 months 18 months 24 months

Mean Change in A1c (%)

Mean Change in A1c

SGLT2 Inhibitor GLP-1 Receptor Agonist

• 1.44
• 0.91
• 0.65
• 0.78
• 0.59
• 0.92

Baseline 6 months 12 months 18 months 24 months SGLT2 (n) 98 88 98 40 17 GLP-1 (n) 210 203 210 133 79

• 1.02
• 0.64

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Results: Secondary Outcomes

• 20
• 15
• 10
• 5

5 10 15 Baseline 6 months 12 months 18 months 24 months

Mean Change in Weight (lbs)

Mean Change in Weight

SGLT2 Inhibitor GLP-1 Receptor Agonist

• 9.2
• 4.3

+11.8

• 11.1
• 15.3
• 6.5
• 10.9

Baseline 6 months 12 months 18 months 24 months SGLT2 (n) 98 94 88 46 19 GLP-1 (n) 210 195 195 123 80

• 7.4

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Results: Secondary Outcomes

• 12
• 10
• 8
• 6
• 4
• 2

2 4 Baseline 6 months 12 months 18 months 24 months

Mean Change in TDD Basal Insulin (units)

Mean Change in Basal Insulin

SGLT2 Inhibitor GLP-1 Receptor Agonist

• 10.2

+2.8

• 8.9
• 1.5
• 4.3
• 4.5

Baseline 6 months 12 months 18 months 24 months SGLT2 (n) 98 95 86 43 12 GLP-1 (n) 210 201 199 98 46

• 3.7
• 2

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Results: Secondary Outcomes

• 20
• 10

10 20 30 Baseline 6 months 12 months 18 months 24 months

Mean Change TDD Bolus Insulin (Units)

Mean Change in Bolus Insulin

SGLT2 Inhibitor GLP-1 Receptor Agonist

+9.7 +12.5 +30

• 8.7
• 15.9

+9.5

• 7.9

Baseline 6 months 12 months 18 months 24 months SGLT2 (n) 98 93 83 37 19 GLP-1 (n) 210 156 152 104 75

• 8.7

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Results: Secondary Outcomes

Change in Blood Pressure, mmHg Baseline 6 months 12 months 18 months 24 months SGLT2i 133/72 130/72 132/73 130/74 136/75 GLP-1 RA 132/74 131/74 131/74 129/72 131/73 Change in eGFR, mL/min/1.73m2 Baseline 6 months 12 months 18 months 24 months SGLT2i 73 67 68 65 68 GLP-1 RA 66 67 66 67 61

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Results: Safety

5 10 15 20 25 30 Retinopathy Yeast Infection Acute Kidney Injury Hypoglycemia Urinary Tract Infection Nausesa/Vomiting

PERCENTAGE (%)

Most Common Adverse Reactions

SGLT2 Inhibitor GLP-1 Receptor Agonist

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Conclusions

• The addition of SGLT2 Inhibitors and GLP-1 Receptor Agonists to basal-

bolus insulin therapy improved glycemic control

• When evaluating data from baseline to twelve months, GLP-1 Receptor

Agonists had a greater impact on:

– Mean A1c reduction – Mean Weight loss – Mean reduction in basal and bolus insulin total daily doses

• Blood pressure and renal outcomes were minimally changed with either

study drug

• Both study drugs were overall well tolerated
• Cost should be taken into consideration with both drug classes

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Acknowledgements

• Additional Authors:
• Tera Raymond, PharmD

– 2018-2019 PGY-2 Ambulatory Care Resident

• Janelle Bouslog, PharmD, BCACP

– Primary Investigator

• Amy Cummings, PharmD, BCACP
• Sarah Will, PharmD, BCPS, BC-ADM
• Connor Rossier, PharmD
• Michael Brown, PharmD Candidate 2021

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References

1. National Diabetes Statistics Report. Centers for Disease Control and Prevention website. https://www.cdc.gov/diabetes/data/statistics/statistics-report.html . Updated July 17, 2017.

• 2. American Diabetes Association. 8. Pharmacologic approaches to glycemic

treatment: Standards of Medical Care in Diabetes – 2010. Diabetes Care. 2010 Jan; 42:S90-102.

• 3. Kalra S. Sodium glucose co-transporter 2 inhibitors: a review of their basic

and clinical pharmacology. Diabetes Ther. 2014 Dec; 5(2): 355-366.

• 4. Tran KL, Park YI, Pandya S, et al. Overview of glucagon like peptide 1

receptor agonists for the treatment of patients with type 2 diabetes. Am Health Drug Benefits. 2017 Jun; 10(4):178-188.

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QUESTIONS?

Contact Information:

Lauren Wilde, PharmD PGY-2 Ambulatory Care Resident Lauren.wilde@va.gov

Kansas City VA Medical Center

4801 Linwood Blvd (119) Kansas City, MO 64128

QUESTIONS?