Dr Bryan Betty. General Practitioner Deputy Medical Director PHARMAC Wellington

Transcription

1 Dr Bryan Betty General Practitioner Deputy Medical Director PHARMAC Wellington 14:00-14:55 WS #113: New Trends in Treating Type 2 Diabetes 15:05-16:00 WS #123: New Trends in Treating Type 2 Diabetes (Repeated)

2 Trends on Type 2 Diabetes New Zealand Dr Bryan Betty Deputy Medical Director PHARMAC GP East Porirua Member National Diabetes Leadership Group, MOH

3 Trends on Type 2 Diabetes New Zealand 1. Context: History/Sugar/Global 2. Burden NZ 3. Prediabetes 4. Left Shift, Differential Mortality, NZ 5. New Medications Acknowledge: Kirsten Coppell, Public Health Physician, Edgar Diabetes Centre Otago, Dr Paul Drury Endocrinologist MOH, Dr Jeremy Krebs Endocrinologist Capital Coast, Dr Wing Cheuk Chan, Public Health Physician, Counties Manukau

4 Type 2 Diabetes Global Epidemic new phenomena? Global Epidemic: Assumed new phenomenon last 50 years Elliot, Joslin Havard: Identified 74 years case records Boston 172 cases amongst 48,000 records Noted: Disease increasing exponentially since mid 1850 s 1921 Joslin: Epidemic to describe what seeing. Statistics show great increase unless this is part explained by better recognition of the disease, the outlook for the disease would be startling.

5 Sugar: Not New? Sugar in the US: Candy, chocolate, ice-cream founded in 1840 s Soft drink Pepsi, Coke 1880 s Per-capita sugar increased 16 fold increase US over century 1920 s: Columbia Emerson, Larimore: suspected refined sugar Rise and fall of sugar consumption followed by similar rises and falls in death rates from diabetes Joslin 1920 s: largely penalty of obesity overconsumption of calories too much food than wrong type of food!! This thinking was widely accepted beyond question rather

6 Sugar: Empty Calories Versus Toxic Robert Lustig: Sugar Toxic 25% of diabetes occur in normal weight, 25% in obese 150 calories a day from sugar 11* increase in diabetes Not about fat it s about how much fat liver has Alcohol and sugar same effect on liver NALD Prof John Sandpiper: Sugar Empty Calories Agree Sugary Soda Drinks - toxic Liquid calories Marker unhealthy lifestyle easier to measure Empty calories Research needed to unpack IDF2015

7 WHO Margaret Chan 2016 : twin epidemics of obesity and diabetes world-wide as a slow-motion disaster Globally IDF: Obesity and diabetes major global issue with climate change and terrorism 1:11 US 1:16 UK Some indigenous populations over 50% adults have diabetes (Pima Indians)

8 Global US: 592 million by million die per year 11% of total world spend on health diabetes related China: 1.9% population 1980, 9.1% today In 2015 noted: Reduction in complications/mortality Mainly educated European men >60 Much less in non-european patients with younger onset diabetes Increasing renal disease.

9 Burden of Disease NZ

10 World wide: Diabetes the long-term trend: 11% health budget and climbing Pharmaceutical Spend NZ

11 Proportion (%) Prevalence of obesity (BMI 30 kg/m 2 ) among New Zealand men and women aged 15+ years 40 Women Men Year Dr Kirsten Coppell Dunedin Ministry of Health New Zealand Health Survey: Annual update of key findings 2012/13. Wellington: Ministry of Health. Ministry of Health New Zealand Health Survey. Annual Data Explorer. minhealthnz.shinyapps.io/nz-health-survey annual-data-explorer/_w_ba211a39/#!/home

12 Age-adjusted relative risk Body mass index at age 18 and age-adjusted risk of diabetes among a cohort of US women aged years in 1976 and followed for 18 years Body mass index (kg/m 2 ) Dr Kirsten Coppell Dunedin Colditz GA, et al. Weight as a risk factor for clinical diabetes in women. American Journal of Epidemiology 1990; 132:

13 Obesity rates As % of total adult population, aged 15 years and over, 2015 * * Obesity Update. OECD (2017) Dr Kirsten Coppell Dunedin

14 Measured overweight (including obesity) among children aged 5-17 years, 2010 or nearest year Obesity Update. OECD. June 2014 Dr Kirsten Coppell Dunedin

15 Diagnosed Approx: 250,000 Total 8.4% NZEO 7.6% Maori 8.8% Pacific 15.7% Focus on Nutrition. Key Findings of the 2008/09 New Zealand Adult Nutrition Survey Dr Kirsten Coppell Dunedin

16 Pre-Diabetes Insights and analyses from Counties Manukau Health on diabetes and cardiovascular disease Dr. Wing Cheuk Chan Public Health Physician, Population Health Team, Counties Manukau District Health Board

17 Not all people with prediabetes are the same: The inclusion criteria for diabetes prevention trials are mainly based on impaired glucose tolerance. HbA1c which is neither sensitive (49%) nor specific (79%) in identifying people with impaired glucose tolerance. Dr. Wing Cheuk Chan, Counties Manukau

18 NZ definitions of prediabetes and diabetes Definition of Pre-diabetes (NZ definition) HbA1c 41 to <50 25% NZ Population Prediabetes US: Prediabetes 38 to 48: would double the number with diagnosis!

19 Testing coverage from Jan 2012 to Dec 2016 Age Maori Pacific Indian Chinese Other Asian Eur/Other Overall % 17% 18% 11% 13% 15% 15% % 16% 24% 13% 14% 20% 18% % 33% 42% 29% 28% 42% 38% % 56% 60% 44% 47% 59% 57% % 68% 71% 60% 61% 65% 66% % 75% 81% 71% 73% 73% 74% % 82% 90% 76% 78% 77% 79% % 88% 94% 81% 83% 81% 83% % 93% 96% 88% 90% 88% 89% % 96% 98% 93% 93% 92% 93% % 97% 98% 95% 96% 95% 96% % 99% 99% 95% 97% 97% 97% % 99% 99% 96% 98% 98% 98% % 99% 99% 97% 98% 99% 98% % 99% 99% 98% 97% 99% 99% % 99% 99% 98% 97% 99% 99% % 99% 98% 98% 100% 99% 99% % 99% 98% 97% 98% 99% 99% Dr. Wing Cheuk Chan, Counties Manukau

20 Prediabetes progression based on NZ criteria: Cut off at HbA1c at 45 will reduce the prediabetes population by 85%. Last HbA1c results Last HbA1c in 2014 only (No. of people) One off high HbA1c ( 50) DM in 3 years Last HbA1c up to 2014 (No. of people) One off high HbA1c ( 50) DM in 3 years 37 12, % 0.86% 18, % 1.00% 38 8, % 0.74% 11, % 0.86% 39 11, % 0.80% 16, % 0.87% 40 14, % 0.94% 19, % 1.13% 41 27, % 0.83% 39, % 0.99% 42 21, % 1.32% 30, % 1.61% 43 16, % 2.13% 22, % 2.54% 44 12, % 3.28% 15, % 3.90% 45 8, % 5.52% 10, % 6.30% 46 5, % 7.91% 7, % 9.22% 47 3, % 13.26% 4, % 14.80% 48 2, % 20.53% 3, % 21.75% 49 1, % 26.99% 1, % 29.48%

21 Overall diabetes risk is small in 2 year from people with prediabetes Age and ethnicity are not strong predictors of progression The best predictor is the latest HbA1c results. Ethnicity % of people with prediabetes progressed to diabetes in 2 years Maori 2.5% Pacific 2.7% Indian 2.3% Chinese 1.5% Other Asian 2.0% Eur/Other 1.4% Unspecified 2.6% Overall 1.8% Dr. Wing Cheuk Chan, Counties Manukau

22 Diabetes Counties Manukau Pre-diabetes progression can be slow: last HbA1c important! More than 9,000 people with poorly controlled diabetes as defined by HbA1c ( 74.9mmol/mol) : 2/3rds of them would remain poorly controlled in the next year 1/3 improve Total number of poorly controlled diabetes remain the same: about 5% of people with diabetes deteriorate each year replacing the 1/3 who improve! >95% of people with poorly controlled diabetes attended primary care in the year, many not for diabetes review: opportunistic versus planned Dr. Wing Cheuk Chan, Counties Manukau

23 Other comments GP s: Provides leadership on issue of clinical inertia: e.g. Dose Titration Practice Skill development, e.g. insulin start. (some practices never start insulin in a year) Specialist support to build capacity and capability in primary care. Opportunistic intervention versus planned Environment Needs environmental and social policies to address the wider drivers of obesity

24 US Diabetes Prevention Study USA: Pre-diabetes: to 44 : 5 year risk 25% 44 to 47: 5 year risk 50% Risk Reduction: Risk reduction over 3 years: Metformin: 31% Intensive Lifestyle: 58% Risk Reduction over 15 years: Durability Metformin 18%, Lifestyle 27% Lower Hba1c to normal at least once: Reduces risk 50% over 10 years. Early intervention key Bariatric Surgery 92% reduction in microvascular esp. renal Dr Leigh Peerault, Colorado, NZSSD 2018

25 Left shift + Differential Mortality

26 Younger Onset Type 2 Diabetes T2DM has historically considered as a disease of adults Worldwide increase in incidence and prevalence of the disease in childhood (onset < 19 years of age) 3 Complications also develop much earlier than in YT1DM 6

27 Prevalence (%) Total diabetes and prediabetes age-specific rates for NZ men and women 60 Prediabetes - men Diabetes - men Prediabetes - women Diabetes -women Age groups (years) Coppell KJ, et al. NZ Med J, 2013 Dr Kirsten Coppell Dunedin

28 Percentage of Diabetics in New Zealand by Age group and Ethnicity: Left Shift 2007 to 2014: Largest relative increase in prevalence Emergence of diagnosis < age 19

29 Relative risk for developing diabetes compared to NZ European

30 Younger Onset Type 2 Diabetes: Major Concern Younger Onset Type 2 diabetes is increasing Major issues world wide indigenous populations intergenerational

31 Global: Indigenous versus Non-indigenous (IDF) Indigenous Indigenous: 80% develop Type 2 diabetes before age of 60 Non-indigenous: 60% develop diabetes >60yrs where ESRF lowest Indigenous population 50-60% all cases ESRF Youth Type 2 10 to 19 year Type 2 emerged mid 90 s Offspring of mother more likely to have type 2 diabetes. Younger the shorter time to complication 14 years (versus 20years older) Need to delay onset!

32 Chronic Kidney Disease + Diabetes NZ Maori and Pacific Progress to ESRF 7-13* rate non indigenous NZ Wide 3000 on Dialysis : 54% Diabetes related 79% South Auckland Dialysis Maori and Pacific Intervention 1% reduction in HbA1c = 37% reduction in microalbumuria Biggest difference is at the point of diagnosis

33 Left shift + Differential Mortality The Burden premature Mortality of Diabetes in New Zealand Ministry of Health Dr Paul Drury 2017

34 The Burden premature Mortality of Diabetes in New Zealand Dr Paul Drury MOH 2017

35 Dr Paul Drury MOH 2017

36 Dr Paul Drury MOH 2017

37 In New Zealand: Left shift in age of diagnosis + Differential Mortality for Maori and Pacific Left shift Younger age: Pacific 4-6* more likely diabetes Shorter time to complication: Pacific, Maori Mortality 4* -7* rate European (40 to 70 years) Renal: 7-13* more likely to progress to ESRD Next generation concern: 20 years to complication: 60+ better outcome than < 60 Early intervention, assertive treatment

38 Younger the age of onset Type 2 Diabetes greater the impact!

39 New Medication + Technology Assoc Prof Jeremy Krebs Capital Coast

40 Type 2 Diabetes Algorithm Diet and Lifestyle No hypos Oral agent But weight gain, heart Good evidence failure, fractures. Oral agent But weight gain, hypos?ihd risk No hypos But GI side effects Metformin Weight neutral Oral agent No hypos Weight loss No hypos But Injectable Weight loss No hypos UTIs SU Glitazone Acarbose DPPIV GLP-1 SGLT2 Insulin DR Jeremy Krebs Wellington

41 Incretins based therapies GPP4 (Oral, Gliptins) GP-1 (Injectable)

42 Glucoregulatory Role of Incretins GLP-1 secreted upon the ingestion of food Promotes satiety and reduces appetite Alpha cells: Postprandial glucagon secretion Beta cells: Enhances glucosedependent insulin secretion Liver: Glucagon reduces hepatic glucose output Stomach: Helps regulate gastric emptying Adapted from Flint A, et al. J Clin Invest. 1998;101: ; Adapted from Larsson H, et al. Acta Physiol Scand. 1997;160: ; Adapted from Nauck MA, et al. Diabetologia. 1996;39: ; Adapted from Drucker DJ. Diabetes. 1998;47: DR Jeremy Krebs Wellington

43 GLP-1 based Medication Not Funded NZ 1. Agents that prolong the activity of endogenous GLP-1 DPP-IV inhibitors 2. Agents that mimic the actions of GLP-1 (incretin mimetics) GLP-1 analogues Drucker DJ, et al. Diabetes Care. 2003;26: ; Baggio LL, et al. Diabetes. 2004;53:

44 DPP4 (Gliptins) Antagonists Adverse Effects Pros No hypoglycaemia Weight neutral Cons Nausea Nasopharyngitis

45 GLP-1 Agonists Adverse Effects Pros No hypoglycaemia Unless combined with other secretalogues Cons Nausea and vomiting Injection Weight loss? Beta cell neogenesis

46 Incretin Therapies and Pancreatitis / Pancreatic Cancer Pancreatitis and pancreatic cancer more common in those with diabetes No convincing evidence that DPPIV antagonists or GLP-1 agonists increase this risk

47 SGLT2 Inhibitors

48 The Kidney and Normal Glucose Handling Majority of glucose reabsorbed Proximal tubule Glucose filtration SGLT2/1 Glucose Minimal to no glucose excretion SGLT: sodium-glucose cotransporter 1. Wright EM, et al. J Int Med 2007;261: Hummel CS. Am J Physiol Cell Physiol 2011;300:C DR Jeremy Krebs Wellington

49 SGLT2 Inhibitors: Insulin-independent approach to remove excess glucose Reduced glucose reabsorption SGLT2 FORXIGA Glucose filtration SGLT2 Inhibitor Glucose Selectively inhibits SGLT2 in the renal proximal tubule 1 FORXIGA 10 mg/day removes approximately 70 g of glucose/day (corresponding to 280 kcal/day) via the urine 2 Increased urinary excretion of excess glucose 1. Gerich JE, Bastien A. Expert Rev Clin Pharmacol 2011;4: FORXIGA ( dapagliflozin propanediol monohydrate) data sheet available at DR Jeremy Krebs Wellington

50 SGLT2 Inhibitors Pros Effect independent of Insulin No hypoglycaemia Weight loss Renal protection Cons Urinary Tract and Genital Infections Ketogenic Bladder and Breast Cancer? BP lowering DR Jeremy Krebs Wellington

51 SGLT-2 EMPA-REG slowed progression ESRD Kidney protection independent of HbA1c Decrease uric acid, weight,bp Ketogenic esp elderly

52 Summary New agents have similar glucose lowering efficacy as older agents Potential Advantages Weight Hypoglycaemia Renal/CVD Unknown long-term effects Cost Cancer

53 New Technology DR Jeremy Krebs Wellington

54 New Technology 25% children on pumps now using More you swipe lower HbA1c Intuitive easy to use Disruptor

55 Summary (1) Sugar: Excess calories versus toxic (Liver) Global slow motion train wreck: 11% total health budget Beware Stats: Decrease in US mortality/morbidity: primarily in European Males >60 Left shift in diagnosis + differential mortality + morbidity Maori and Pacific: 6* more likely to be diagnosed diabetes 40 and 55yrs 7* more likely to die diabetes 40 to 70 years 7-13* more likely to progress to ESRF

56 Summary (2) Pre-diabetes Biggest predictor progression HbA1c 45 to 50 Get back to normoglycemia once half progression Delaying Onset Key: Metformin + Lifestyle Younger Onset Reduced time to complication (14 years versus 20years) Assertive approach New Medication will have a place Primary Care: Opportunistic versus proactive care Clinical inertia

57 Questions