Prediabetes: Metformin vs. Lifestyle Intervention Tannaz Moin, MD, MBA, MSHS

Transcription

1 Prediabetes: Metformin vs. Lifestyle Intervention Tannaz Moin, MD, MBA, MSHS Assistant Professor, David Geffen School of Medicine at UCLA Division of Endocrinology, Diabetes and Metabolism HSR&D Center for the Study of Healthcare InnovaEon, ImplementaEon & Policy VA Greater Los Angeles Healthcare System

2 I have no conflicts of interest to disclose

3 Outline Prediabetes DefiniEon, controversies and emerging data MeIormin and lifestyle interveneon for type 2 diabetes preveneon TranslaEon in real- world pracece

4 Prediabetes Intermediate metabolic state with abnormally elevated blood sugars Diagnos)c thresholds? Medicaliza)on of risk? To treat or not to treat? Prevent vs. delay?

5 Exis8ng Controversies Tests and diagnosec thresholds: FPG (mg/dl) 2 hour OGTT (mg/dl) HbA1c (%) Type 2 Diabetes 126 Type 2 Diabetes 200 Type 2 Diabetes 6.5 Prediabetes Prediabetes 140 Prediabetes Normal Normal Normal Diabetes Care 2016 Jul; 39(7): Prevalence Risk for progression to type 2 diabetes Risk of micro- and macrovascular complica8ons

6 Emerging Data Microvascular: associaeon cited in numerous studies Macrovascular: meta- analysis of 53 prospeceve studies é risk CV events (35 studies) and CHD disease (24 studies) with IFG, IGT and HbA1c % é risk all cause mortality (25 studies) and stroke (18 studies) with IFG and IGT but not HbA1c % Healthcare uelizaeon: 1.3x rates of hospitalizaeon Prevalence rising worldwide Racial and ethnic dispariees Lancet. 2012;379. BMJ 2016;355:i5953 Diabetes Care 2016 Mar; dc Policy Brief UCLA Cent Health Policy Res Mar;(PB2016-1):1-8

7 Growing Public Health Concern 1 in 3 US adults have prediabetes 15-30% Percentage who will transieon to type 2 diabetes in 5 years

8 MeWormin vs. Lifestyle Interven8on

9 The Diabetes Preven8on Program (DPP) Study Double blind randomized trial 3,234 parecipants from 27 centers in the US Mean age 50.6 years and BMI 34.0 kg/m % women, 45.3% minoriees FPG mg/dl and OGTT 75g, 2hr mg/dl DPP Placebo MeIormin 850mg BID Intensive Lifestyle 16 one- on- one sessions Goals = 7% weight loss, >150 min/wk moderate acevity

10 DPP Results 40 Placebo Cumulative Incidence of Diabetes (%) Year Metformin Lifestyle Figure 2. Cumulative Incidence of Diabetes According to Study Group. The diagnosis of diabetes was based on the criteria of the Intensive lifestyle was most effeceve By subgroup, meiormin more effeceve if: FPG >110 mg/dl Age <60 years BMI >35 kg/m 2 N Engl J Med, Vol. 346, No. 6

11 Diabetes Prevention Program. Lancet. 2009;374: Lancet Diabetes Endocrinol 2015;3: DPP Outcomes Study (DPPOS) Follow- Up Results DPP DPPOS Cumula8ve incidence of diabetes (%) 10 Years L = 34% M = 18% 15 Years L = 27% M = 18% 2.8 Years L = 58% M = 31% Time since DPP randomiza8on (years)

12 Addi8onal DPP Findings Intensive lifestyle lost the most weight, but partly regained; meiormin maintained modest weight loss Heterogeneity of effect by age and subgroup Reversion to normal glycemia was associated with lower rates of progression to type 2 diabetes Lifestyle and meiormin had similar effect in preveneng HbA1c- defined diabetes Quality of life é with lifestyle but not meiormin Lifestyle cost- effeceve, meiormin marginally cost- saving vs. placebo Lancet Jun 16; 379(9833): Diabetes Care 2015 Jan; 38(1): Ann Intern Med. 2005:142: Diabetes Care. 2012;35:

13 MeIormin + Lifestyle IntervenEon

14 Stepwise Approach: Diabetes Community Lifestyle Improvement Program (D- CLIP) Randomized, controlled, translaeonal trial 578 Asian Indian adults Mean age 44.4 years and BMI 27.9 kg/m 2 IGT, IFG or IGT+IFG D- CLIP Diabetes Care 2016 Aug; dc Control DPP Lifestyle + MeIormin 500mg BID At 4 months, those with IFG +IGT and IFG and HbA1c>5.7% were prescribed meiormin

15 Diabetes Care 2016 Aug; dc Stepwise Approach: Diabetes Community Lifestyle Improvement Program (D- CLIP) Mean weight loss = 4% at 6 months Over 3 years of follow- up, 32% relaeve risk reduceon (RRR) with lifestyle + meiormin Diabetes incidence 34.9% control vs. 25.7% lifestyle + meiormin, p=0.014 Heterogeneity of effect across prediabetes subtypes: IGT+IFG>IGT>IFG Number needed to treat (NNT) to prevent one case of diabetes = 9.8

16 Other Trials Examining MeWormin + Lifestyle Interven8on Study, Year, Country Design Criteria N=total (n=met) Followup (Years) Arms Relative Risk Reduction IDPP, 2006 India RCT IGT Age (n=136) 2.5 1=control 2= L 3= M mg BID 4= L+ M mg BID L = 28.2% M = 26.4% L + M = 28.2% Andreadis et al, 2009 Greece RCT BMI>27 Age> (n=95) 1 1= L (control) 2= L + M L+M = 7% all (18.5% with predm) Iqbal et al, 2012 Pakistan RCT IGT 317 (n=95) 1.5 1= Control 2= L 3= L+ M 500mg BID L = 71% L + M = 76.5% SystemaEc Review of MeIormin Use for Type 2 Diabetes PrevenEon. Under Review

17 Efficacy Summary Lifestyle MeWormin Lifestyle + MeWormin Higher relaeve risk reduceon overall More effeceve in higher risk subgroups Similar to placebo in those >60 years Safety No side effects Good safety profile (GI, B12) Cost Cost- effeceve Marginally cost- saving? Feasibility Resource intensive Rx readily available? Other Considera8ons Benefits beyond diabetes preveneon No FDA indicaeon NNT over 3 yrs More effeceve in higher risk subgroups (IFG+IGT) Same Same

18 Lifestyle Are We Transla8ng Evidence into Prac8ce? Numerous real world translaeonal studies Uptake and reach remain a criecal challenge MeIormin Efforts to translate this arm of the DPP have been limited Extremely low rates of use à 3.7% of insured working age adults with prediabetes were prescribed meiormin Ann Intern Med. 2015;162(8): CDC Prediabetes Could it Be You? 2016

19 Prevent Diabetes STAT Public health campaign launched by CDC and AMA Healthcare Provider Toolkit Methods to screen and refer high- risk paeents to CDC- recognized community based or virtual DPP in their communiees

20 Changing Real World Prac8ce Refer paeents with prediabetes to CDC recognized DPP lifestyle interveneons (preferred) Consider meiormin for diabetes preveneon in high risk paeents: age <60 years, BMI>35 kg/m 2, and women with prior gestaeonal diabetes Monitor for development of diabetes annually Screen and treat modifiable risk factors for CVD ADA Standards of Care 2016

21 Changing Real World Prac8ce Increase prediabetes awareness Prediabetes- aware adults are more likely to engage in lifestyle change interveneons Help paeents make informed choices that are aligned with their preferences and values OpportuniEes to promote paeent- centered dialogue about prediabetes in primary care PaEents may consider both intensive lifestyle and meiormin as acceptable treatment opeons UCLA MyMeds pharmacist consults available in EPIC Diabetes Educ Dec;42(6):

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23 Thank You! Research Funding Acknowledgement: