New Diabetes Medications - Elizabeth Seaquist MD Director, Division of Endocrinology and Diabetes - MHealth.org
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New Diabetes Medications
Elizabeth Seaquist MD
Director, Division of Endocrinology and Diabetes
Vice Chair for Clinical Affairs
Department of Medicine
Pennock Family Chair in Diabetes Research
University of Minnesota
Presenter Disclosure Have served as consultant to Sanofi, Novo Nordisk, Lilly, MannKind, WebMD, and Zucera and obtained research support from Lily I am a current member of the ABIM Internal Medicine Exam Committee. To protect the integrity of Board Certification, ABIM enforces strict confidentiality and ownership of exam content. As a member of an ABIM exam committee, I agree to keep exam information confidential. As is true for any ABIM candidate who has taken an exam for Certification, I have signed the Pledge of Honesty in which I have agreed not to share ABIM exam questions with others. No exam questions will be disclosed in my presentation.
Outline • 2018 ADA/EASD guidelines for the management of hyperglycemia in type 2 diabetes • Basal insulins
Management of Hyperglycemia in
Type 2 Diabetes 2018—A Consensus
Report by the ADA and EASD
• Evidence based consensus report presented a EASD in Oct
2018
• In print in Diabetes Care, Diabetologia November 2018
• Greater focus on lifestyle interventions, with increased
emphasis on weight loss and obesity management, including
metabolic surgery
• Greater focus on patient related issues and self-management
which have a major impact on success of any pharmacological
interventions
Copyright ADA & EASD
2018
Foundational therapy is metformin
and comprehensive lifestyle
management (including weight
management and physical activity)
Copyright ADA & EASD
2018
Consensus Recommendation —
New since 2015
Consider important comorbidities that should influence
the choice of a particular glucose-lowering medication
Among patients with type 2 diabetes with established
atherosclerotic cardiovascular disease (ASCVD), sodium-
glucose cotransporter 2 (SGLT2) inhibitors or glucagon-
like peptide 1 (GLP-1) receptor agonists with proven
cardiovascular benefit are recommended as part of
glycemic management
Copyright ADA & EASD
2018
CHOOSING GLUCOSE-LOWERING
MEDICATION IN THOSE WITH ESTABLISHED
ASCVD OR CKD
Copyright ADA & EASD
2018
If ASCVD Predominates:
GLP-1 receptor agonist with
proven cardiovascular benefit
• Liraglutide > semaglutide
> exenatide LAR
SGLT2 inhibitor with proven
cardiovascular
benefit
• Empagliflozin >
canagliflozin
Copyright ADA & EASD
2018Caveats and
Questions
No evidence of CVD
benefit in those at
lower cardiovascular
risk
The combination of
SGLT2-i and GLP-1 RA
has not been tested in
cardiovascular outcome
trials
Copyright ADA & EASD
2018CHOOSING GLUCOSE-LOWERING
MEDICATION IN THOSE WITH ESTABLISHED
HF OR CKD
Copyright ADA & EASD
2018Among patients with ASCVD in whom HF coexists
or is of concern, SGLT2 inhibitor are
recommended
Rationale: Patients with T2D are at
increased risk for heart failure with
reduced or preserved ejection
fraction
Significant, consistent reductions in
hospitalization for heart failure
have been seen in SGLT2 inhibitor
trials
Caveat: trials were not designed to
adjudicate heart failure
Majority of patients did not have
clinical heart failure at baseline
Copyright ADA & EASD
2018Consensus Recommendation:
For patients with type 2 diabetes and CKD, with or without
cardiovascular disease, consider the use of an SGLT2
inhibitor shown to reduce CKD progression or, if
contraindicated or not preferred, a GLP-1 receptor agonist
shown to reduce CKD progression .
Several of these medications have demonstrated renal
benefit and cardiovascular benefit and should be considered
as part of treatment
Copyright ADA & EASD
2018CKD Considerations For SGLT2-i adequate eGFR differs between countries and compounds SGLT2-i are registered as glucose-lowering agents to be started if eGFR>45-60 ml/min/1.73m2 and stopped at eGFR 45-60, as glucose-lowering effect declines with eGFR SGLT2-i CVOTs included patients with eGFR>30, and there were no excess adverse events in subjects with eGFR
Copyright ADA & EASD
2018Consensus Recommendation: In patients who need the greater glucose-
lowering effect of an injectable medication, GLP-1 receptor agonists are the
preferred choice to insulin for reasons or better A1c and weight outcomes
in clinical trials. For patients with extreme and symptomatic hyperglycemia,
insulin is recommended.
Abd El Aziz MS et al. Diabet Obes Metab 2017
Copyright ADA & EASD
2018Outline • 2018 ADA/EASD guidelines for the management of hyperglycemia in type 2 diabetes • Basal insulins
Basal insulin strategies
NPH
• Variable absorption, pronounced peak, 10-20 hour duration
• Requires 2x daily administration to provide 24 hour coverage
Detemir
• Twice daily dosing with less variability than NPH
• Sometimes give once a day
U100 Glargine
• Relatively constant peakless concentration over 24 hours
• Once daily administration at same time each day
U300 Glargine and Degludec
• New basal insulins with prolonged duration of action and stable/flat
glucose lowering effect over 24 hour period
• Require 3+ days to get to steady state
• Administered as daily injection that need not be precise in timingWhich basal insulin should
you use?
• SWITCH 1 and SWITCH 2 showed patients had less
hypoglycemia when they received randomized
treatment with degludec vs. glargine (both published
in JAMA 2017)
• DEVOTE study demonstrated that T2DM subjects
randomized to degludec had less hypoglycemia,
mortality, and CVD events than subjects randomized
to glargine (NEJM 2017)
• BRIGHT trial randomized T2DM subjects to degludec
vs. U300 glargine. Essentially no difference in risk of
hypoglycemia (Diabetes Care 2018)
Copyright ADA & EASD
2018Summary • Patient-centered decision-making and support and consistent efforts at improving diet and exercise remain the foundation of all glycemic management. • The management of hyperglycemia in type 2 diabetes has become complex with the number of glucose-lowering medications now available. • Initial use of metformin, followed by addition of glucose-lowering medications based on patient co-morbidities and concerns is recommended.
Thank you!
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