Systematically Assessing the Promise of Type 2 Diabetes Remission Is this the Next Frontier of Diabetes Care? Hertzel C. Gerstein MD MSc FRCPC McMaster University & Population Health Research Institute HCG 2017
Disclosures Grants/Research Support: Consulting: Speakers Honoraria: Sanofi, Lilly, AstraZeneca, Merck Sanofi, Lilly, AstraZeneca, Merck, Novo Nordisk, Abbot, Amgen, Boehringer Ingelheim, Teva Sanofi, Lilly, AstraZeneca, Novo Nordisk, Abbot, Boehringer Ingelheim
Outline Burden of type 2 diabetes Current type 2 diabetes management paradigm What about remission? Lessons learned from prevention What s in it for insurers? The network
Outline Burden of type 2 diabetes Current type 2 diabetes management paradigm What about remission? Lessons learned from prevention What s in it for insurers? The network
Diabetes around the world One in 2 adults with diabetes are not diagnosed
Diabetes around the world
Diabetes around the world
In 1980: 108 M adults over 18 Age Standardized Rates = 5% of women & 4% of men In 2014: 422 M adults over 18 Age Standardized Rates = 8% of women & 9% of men
Male Diabetes Prevalence 1980
Male Diabetes Prevalence 2014
Female Diabetes Prevalence 1980
Female Diabetes Prevalence 2014
The Patient s Burden of Diabetes Symptoms of Hyperglycemia plus: Blindness Cataracts Kidney Failure Nerve Damage/Pain Foot pain, ulcers Leg/Foot Amputations MI/Strokes PVD NASH/Cirrhosis Cancers Cognitive Decline Depression Hip Fractures Imbalance & Frailty Joint Complaints Erectile Dysfunction Sexual Dysfunction Infertility Gut Problems
Outline Burden of type 2 diabetes Current type 2 diabetes management paradigm What about remission? Lessons learned from prevention What s in it for insurers? The network
Managing Type 2 Diabetes Modifications to diet & increases in physical activity Metformin (if tolerated) Other glucose-lowering drugs, started & stopped on the basis of: Formularies Reimbursement policies Local opinion leaders Personal experience/anecdotes Experience & perceptions of early adopters Share of voice Nonglycemic preventive care
Treat-to-Failure Approach Educate Start lifestyle with/without drug therapy Target an appropriate HbA1c (generally < 7% but varies) Follow Wait until G levels rise & therapy is no longer working (i.e. failing) Reinforce lifestyle & adherence, make deals, procrastinate Intensify therapy by increasing dose, replacing, or adding drugs Follow until fails again
Implications of Treating-to-Failure A diabetes diagnosis is the beginning of a lifelong, increasingly complex journey of failure & ever-increasing complexity & cost Hassle of glucose testing Lifelong labeling with the diagnosis & associated moral stigmata Exposure to harms of hyperglycemia & hypoglycemia Exposure to the long-term & mainly unknown risks of glucoselowering drug therapies & drug interactions Lots of non-adherence to lifelong therapies Frustrating for everyone (futility problem just grows)
Outline Burden of type 2 diabetes Current type 2 diabetes management paradigm What about remission? Lessons learned from prevention What s in it for insurers? The network
Definition of Remission..& Regression ADA Definition (Diabetes Care 2009) Partial: HbA1c<6.5% (or FPG <7) & no drugs X 1 year Complete: HbA1c <5.7% (or FPG <5.6) & no drugs X 1 year Prolonged: > 5 years Possible Alternatives Partial Remission: HbA1c <6.5% & no drugs for some period of time Complete Remission: HbA1c <6.0% & no drugs for some period of time Regression: HbA1c <7.0% & no drugs for some period of time
Evidence for Remission Diabetes can be prevented so the progression of dysglycemia can be changed Experience with bariatric surgery: > 60% remission rates Lifestyle-based therapy: Allocation to 5% weight loss & 150 min activity/week in the LOOK AHEAD trial.. 11.5% remission rates at 1 year & 7.5% at 4 years (vs. ~ 2% in controls) Reduced need for glucose lowering & BP drugs Intensive insulin for < 6 weeks 2 year remission rates > 40%
Limited Intensive Insulin & Remission Kramer et al. Lancet Diabetes & Endocrinology 2013;1:28 Citation Year N Design IIT Regimen Days
Evidence for Remission Diabetes can be prevented so the progression of dysglycemia can be changed Experience with bariatric surgery: > 60% remission rates Lifestyle-based therapy: Allocation to 5% weight loss & 150 min activity/week in the LOOK AHEAD trial.. 11.5% remission rates at 1 year & 7.5% at 4 years (vs. ~ 2% in controls) Reduced need for glucose lowering & BP drugs Intensive insulin for < 6 weeks 2 year remission rates > 40% ACCORD participants in the intensive group maintained better glucose levels than controls despite relaxation of therapy
Persistent Normal G in ACCORD Effect of ~ 4 years of Intensive G therapy on Future Glycemia Punthakee et al. Diabetologia 2014
Attractiveness of Remission: Patient Concept of Metabolic Rehabilitation Lifestyle approaches will be the foundation of any regimen & will be combined with short term use of drugs Promise of staying off drugs is a strong incentive to maintain lifestyle changes Costs of short-term drug use are less Self-efficacy is high May reduce long-term consequences e.g. long-term effects of prevention
20 Yr Risk of Severe Retinopathy Laser, Blindness or Proliferative Retinopathy HR 0.53; 95%CI (0.29, 0.99); P=0.048 After adjusting for DM duration, HR = 0.85 (0.47, 1.54); p=0.6 Da Qing Trial. Diabetologia 2011; 54:300
23 Year Risk of Death, CV Death & Diabetes Death HR 0.71 (0.51, 0.99) Passive follow-up of the Chinese Da Qing diabetes prevention trial CV Death HR 0.59 (0.36, 0.96) Diabetes HR 0.55 (0.40, 0.76) Da Qing Trial. Lancet D&E 2014; 54:300
Remission Regimens Being Tested Multifaceted McMaster/PHRI Approach Remission induction, & then follow-up for relapse Coaching & frequent (e.g. weekly) interactions with team Specific dietary composition: calories + nuts, oils, fibre, etc Moderate activity Intensive G lowering drugs targeting normal G levels that prevent diabetes (e.g. insulin, metformin, other drugs, combinations) Nonglycemic therapies that can affect beta cell health/insulin action (e.g. salicylates, anti-inflammatory drugs, RAS drugs) Time limited use of drugs Treatment of relapse
Pilot Trial McInnes et al. JCEM 2017;102:1596 Randomized 83 pts with type 2 diabetes < 3 y on 0-2 oral agents to Standard diabetes care 2-month intensive metabolic intervention 4-month intensive metabolic intervention Intensive metabolic intervention: Frequent meetings with team (weekly) Physical activity & diet Metformin, insulin glargine targeting normoglycemia, & acarbose Outcomes Feasibility (recruitment, adherence, retention) Partial or complete remission off diabetes drugs
Pilot Trial McInnes et al. JCEM 2017;102:1596 Remit @ 3 Mo. (No Drugs) 8 Week Group 16 Week Group Complete (A1c<6%) RR =3 (11% vs. 4%) RR=2 (15% vs. 7%) Partial/Complete (A1c<6.5%) RR=2 (21% vs. 11%) RR=3 (41% vs. 14%) Regression/Remission (A1c<7%) RR = 2 (29% vs. 14%) RR=3 (48% vs. 14%)
Outline Burden of type 2 diabetes Current type 2 diabetes management paradigm What about remission? Lessons learned from prevention What s in it for insurers? The network
Why not Just Focus on Prevention? People are reluctant to take proven preventive therapies & this is reinforced in the media, internet, social media It will never happen to me They cause other problems Industry & doctors want to scare me into taking this so they can profit Don t know if prevention is working if the disease is prevented Adherence is a problem Many unregulated products with high market presence Examples. Vaccination for anything Statins (perceived as prevention) vs. ACE-inhibitors (perceived as Rx) Metformin to prevent diabetes
Outline Burden of type 2 diabetes Current type 2 diabetes management paradigm What about remission? Lessons learned from prevention What s in it for insurers? The network
What s in it for Insurers? Time-limited drug use may mean lower drug costs Need for complex long-term multiple drug regimen may be replaced by intensive but short-term therapy with a limited drug regimen Successes more companies & researchers improved remission rates Pts will have a strong incentive to maintain lifestyle changes after stopping drugs They will have firsthand experience with the benefits of intensifying therapy Potential benefits on well-being, sleep apnea, BP, back pain Work productivity may increase & absenteeism decrease Insurance company support for a proven remission program may provide that company a competitive advantage patients may want to access such programs for remission & for treating relapse
Outline Burden of type 2 diabetes Current type 2 diabetes management paradigm What about remission? Lessons learned from prevention What s in it for insurers? The network methodically testing remission regimens in RCTs
Remission Evaluation of Metabolic Interventions in Type 2 Diabetes Diabetes May Not Have be Forever!