Management of Diabetes in the Older Person Nicola Zammitt CD ECED Secondary care lead Diabetes MCN 30/3/17

Outline of workshop What are the benefits of tight glycaemic control? Is tight glycaemic control a bad thing? What will make a difference to life expectancy? Are there guidelines/targets for older people? Which drugs should we choose? What else would anyone like to discuss?

Benefits of tight glycaemic control Relief of symptoms Reduction of complications UKPDS 33 Lancet 1998

Benefits of tight glycaemic control Relief of symptoms Reduction of complications 0 3 6 9 12 15 UKPDS 33 Lancet 1998 Time since randomisation (yrs)

Benefits of tight glycaemic control Relief of symptoms Reduction of complications UKPDS 33 Lancet 1998 Time since randomisation (yrs) 0 3 6 9 12 15

Benefits of tight glycaemic control Relief of symptoms Reduction of complications UKPDS 33 Lancet 1998

Benefits of tight glycaemic control Relief of symptoms Reduction of complications UKPDS 10 yr FU NEJM 2008

Benefits of tight glycaemic control Relief of symptoms Reduction of complications UKPDS 10 yr FU NEJM 2008

Benefits of tight glycaemic control Relief of symptoms Reduction of complications UKPDS 10 yr FU NEJM 2008

Benefits of tight glycaemic control Relief of symptoms Reduction of complications UKPDS 10 yr FU NEJM 2008

Benefits of tight glycaemic control Relief of symptoms Reduction of complications UKPDS 10 yr FU NEJM 2008 Loss of HbA1c between-group differences “Legacy effect” ? Benefits of early control

Benefits of tight glycaemic control Relief of symptoms Reduction of complications Evidence of benefit for microvascular disease ? Legacy effect for macrovascular disease Long time to see benefits (esp macrovascular) Patient age Comorbidities What complications are we trying to prevent?

Hypoglycaemia in type 2 DM Risk of hypo increases with increasing insulin deficiency and duration of insulin treatment Regardless of treatment modality, intensive therapy associated with increased risks of hypo Insulin-deficient patients with T2DM can develop syndromes such as IHA and HAAF IHA increases risk of SH. Older patients are at increased hypo risk as a result of diminished symptoms and altered thresholds for counterregulatory responses Knowledge of hypoglycaemia is poor in the elderly and their relatives 1. Leese GP, Wang J, Broomhall J, Kelly P, Marsden A, Morrison W, et al. Frequency of severe hypoglycemia requiring emergency treatment in Type 1 and Type 2 diabetes: a population-based study of health service resource use. Diabetes Care 2003;(1176):1180. 2. Donnelly LA, Morris AD, Frier BM, Ellis JD, Donnan PT, Durrant R, et al. Frequency and predictors of hypoglycaemia in type 1 and insulin-treated type 2 diabetes: a population based study. Diabetic Medicine 2005;22:449-55.

Hypoglycaemia in type 2 DM Study Hepburn 1993 VA-CSDM, 1995 UKPDS 33, 1998 Henderson, 2003 Leese, 2003 Leiter 2003 Donnelly, 2005 Akram, 2006 UK Hypoglycaemia Study Group, 2007 Schopman, 2010 Design Retrospective questionnaire Prospective multicentre RCT Population-based dataset analysis Retrospective recall of SH Prospective Prospective observational multicentre study Retrospective recall of SH, prospective FU of mild hypos No 104 T1DM, 104 T2DM 153 3935 215 160 335 total; 133 T2DM 94 T1DM 173 T2DM 401 85 T2Ins <2 105 T2 Ins >5 122 Durn 1 year 18-35 months 10 years I year Cross-sectional 1 month One month All hypos 82.7% 56% conv 93% intsv 36.5% 64% - 72.9% 45% 51% T2 Ins <2 64% T2Ins >5 SH 10% NA 2.3% 15% 7.3% 14.3% 3% 16.5% 7% T2Ins <2 25% T2Ins >5 Overall 9.8% (NHA 2.7% IHA 50%)

Hypoglycaemia in type 2 DM 25% 22% UK Hypoglycaemia Study group Diabetologia 2007

Morbidity of hypoglycaemia in type 2 DM Different symptoms in elderly (eg mimic CVA) Hypos can precipitate vascular events T2DM pts need SAS at least as often as T1DM Leese et al, Diabetes Care, 2003: 244 SH episodes in 160 people over 1yr in Tayside. Emergency Rx needed for 7.1% of T1DM, 7.3% of insulin-treated T2DM and 0.8% of people on OHAs Donnelly et al, Diabetic Medicine 2005: 267 people in Tayside with insulin-treated DM, FU for 1/12. 45% prevalence all hypo in insulin-treated T2DM Only 10% of T1DM with SH needed emergency services vs 30% of T2DM 1. Leese GP, Wang J, Broomhall J, Kelly P, Marsden A, Morrison W, et al. Frequency of severe hypoglycemia requiring emergency treatment in Type 1 and Type 2 diabetes: a population-based study of health service resource use. Diabetes Care 2003;(1176):1180. 2. Donnelly LA, Morris AD, Frier BM, Ellis JD, Donnan PT, Durrant R, et al. Frequency and predictors of hypoglycaemia in type 1 and insulin-treated type 2 diabetes: a population based study. Diabetic Medicine 2005;22:449-55.

T2DM Old Age Hypoglycaemia Cognitive decline and dementia Frailty Renal dysfunction Increased mortality Institutionalisatio T2DM Old Age Hypoglycaemia Decreased symptoms Impaired counter regulation Tight glycaemic control Polypharmacy Decreased microvascular complications. No effect on macrovascular complications. Mobility limitation and decline in physical function Falls Fractures

Guidelines on glycaemic targets in older pts

Guidelines on glycaemic targets in older pts

SGLT2 inhibitors: mode of action independent of beta cells T2DM therapies Targets insulin resistance Targets insulin deficiency Diet and lifestyle Insulin secretagogues Metformin Insulin Glitazones (TZDs) DPP-IV inhibitors GLP-1 analogues SGLT2 inhibitors: mode of action independent of beta cells

T2DM therapies Pioglitazone: DPP-IV: GLP-1: SGLT2: No hypos Wt gain, oedema, osteoporosis, ? Bladder cancer DPP-IV: No hypos, weight neutral Not very potent. Reduce in renal impairment GLP-1: No hypos, weight loss GI side effects, ? Pancreatitis, care in renal impairment, injections (but weekly formulation available) SGLT2: No hypos, weight loss, BP,  CV death (empagliflozin) Need normal renal function. Not recommended in elderly

Guidelines on glycaemic targets in older pts European Diabetes Working Party for Older People

Clinical guidelines elderly T2DM

Discussion