DM Management in Elderly- What are the glucose targets?

DM Management in Elderly- What are the glucose targets? AFSHAN ZAHEDI, BASC, MD, FRCP(C) ENDOCRINOLOGY WOMEN S COLLEGE HOSPITAL ASSISTANT PROFESSOR OF MEDICINE UNIVERSITY OF TORONTO NOVEMBER 2, 2011

Disclosures No Financial interest or investment in any Pharmaceutical company Advisory Boards for Amgen, Eli Lilly, GSK, Merck, Medtronics, Novartis, Novo- Nordisk, and Sanofi-Aventis CME programs for Amgen, Bristol-Myers Squibb, Eli Lilly, GSK, Merck, Novo- Nordisk, Novartis, Pfizer and Sanofi-Aventis

Objectives Differentiate aspects of DM in Geriatric population Review the current evidence on relation of glycemic control and DM complications Review current International Guidelines Suggest appropriate glycemic targets for geriatric patients Review Type 2 Diabetes treatment options in elderly Discuss the risks & the importance of eliminating hypoglycemia in geriatric patients

Prevalence of DM Prevalence of DM rises with age and higher in men than in women. 15 % of women and 20 % men over 75 have diagnosed diabetes and this number increases to 25% in ethnic groups. 1 out of 4 residents of LTC in Ontario have diabetes Aging population & immigration from areas with highest prevalence of diabetes in the world 1.Ontario Diabetes Database, 2. Diabetes Care 1998;21:518 3. Diabetes in Ontario; An ICES Practice Atlas 2003

Rational for Glycemic Management in Elderly Elderly with Diabetes have higher rates of: Functional disability Premature death Coexisting illness Hypertension Coronary heart disease Stroke JAGS 51:S265 2003

Rational for Glycemic Management in Elderly Increase in common Geriatric Syndromes is seen in older patients with diabetes: Cognitive impairment Urinary incontinence Injurious falls Persistent pain Depression Polypharmacy JAGS 51:S265 2003, Diab Care 20:585 1997, Diab Med 1:S41, 1998

Barriers in setting Glycemic Targets in Geriatric Population Variable life expectancies Clinical heterogeneity Functional heterogeneity Lack of Grade A evidence Exclusion of Frail Elderly from large RCTs Individualize Goals for DM management

Main Goals of Treatment Improvement of quality of life Prevention of onset of ACUTE complications of DM Severe and recurrent hypoglycemia Severe and prolonged hyperglycemia Acute Side-effects of treatment regimens Improve quality of work for care-givers

Higher risk of Acute Complications Hyperglycemia ( > 14 mmol/l) Impaired renal function Decrease in thirst drive Acute changes in volume status Hypoglycemia (< 4.0 mmol/l) Decrease in hypoglycemia awareness Associated cognitive impairment Risk of falls fractures 1 Increase risk of Mortality 2 1. JCEM 86:32 2001, 2. ACCORD, NEJM 2008

Glucose Targets in Older Adults with Type 2 diabetes

A1C Average BG (3 months) weighted to the past month Limitations

Other limitations to A1C Hemoglobinopathies Sickle cell or Thalassemia trait Large blood loss Transfusions Low hemoglobin and low hematocrit may result in inaccurate A1C levels May be due to renal disease Alternate testing: Fructosamine, past 4-21 days BG control

CDA Glycemic Targets 2008 For most patients A1C (%) 7.0 (< 6.5% to lower nephropathy if can be safely done) Preprandial PG (mmol/l) 2-h postprandial PG (mmol/l) 4.0-7.0 5.0-10.0 (5-8 if A1c not achieved with above) Elderly. In people with multiple comorbidities, a high level of functional dependency and limited life expectancy, the goal should be less stringent, and clinicians should try to avoid symptoms of hyperglycemia and prevent hypoglycemia CDA CPG 2008

Intensive Glycemic Control - RCTs UKPDS: Mean age 54 (N=3867) 1 A1C 7% vs 7.9% 37% reduction in microvascular complications 21% reduction in any endpoint related to DM ADVANCE: Mean age 66 (N=11140) 2 32% CVD at baseline A1C 6.5% vs 7.3% No difference in retinopathy, CVD or mortality VADT: Mean age 60 (N=1792) 3 40% CV events A1C 6.9% vs 8.4% No significant difference in CVD or microvascular complications 1. Lancet 325:837-53, 1998, 2.NEJM 2008 3.NEJM 2009

Intensive Glycimic Control - RCTs ACCORD: Mean Age 62 (N=10251) 1 35% CV events at baseline A1C 6.4 % vs 7.5 % Increase risk of death from CV disease and all cause mortality Hypoglycemia in ACCORD 2 Intensive glycemic control results in increase rate of severe hypoglycemia (glucose < 2.8 mmo/l ) Patients with T2DM who have severe hypoglycemia are at increase risk of death regardless of intensity of glucose control 1. NEJM 2008, 2. BMJ 339:B4909 2009

Diabetes and Aging Study Retrospective cohort study (2004-8) N = 71,092 - T2DM age > 60 Identify glycemic levels with the lowest rates of complications and mortality in older patients Mortality had a U-Shape relationship with A1C Suggest: setting an A1C < 8 % and caution that A1C <6 % were associated with increased mortality Diab Care 34(6):1329 2011

Glycemic Targets DM GUIDELINES FOR GERIATRIC PATIENTS

Guidelines American Geriatric Society The American Geriatrics Society recommends a slightly higher A1C for certain groups: for frail older adults, persons with life expectancy of less than 5 years, and others in whom the risks of intensive glycemic control appear to outweigh the benefits, a less stringent target such as A1C 8% is appropriate. JAGS 51:S265 S280, 2003 18

Guidelines: Veterans Affairs & DoD Major Comorbidities or Physiological Age Absent (>15 years of life expectancy) Present 5 to 15 years of life expectancy Marked < 5 years of life expectancy Microvascular Complications Absent or Mild Moderate Advanced 7 % <8% <9% < 8% <8% <9% <9% <9% <9% 1.VA/DoD Clinical Practice Guideline for The Management of DM 2010 19

European Union Geriatric CPG European Diabetes Working Party for Older People. (2001-2004). CPG for type 2 diabetes mellitus

Glycemic Targets FPG or preprandial PG CPG 2008 1 Frail elderly Consider 4-7 mmol/l 7.0-9.1 mmol/l 2 2 hours postprandial 5.0 10.0 mmol/l ( 5-8 if A1C target not met) In the low teens (< 14 mmol/l) 1 A1C (%) < 7% (< 6.5% to lower nephropathy if can be safely done) < 8% 2 1. Canadian Diabetes Association 2008 Clinical Practice Guidelines 2. European Union Geriatric Society 2004, American Geriatic Society 2003, VA DoD 2010

Goals of Treatment Reduce fluctuations in glucose levels Avoid hypoglycemia when possible Choose OHA with less risk of hypoglycemia as your second line of therapy after Metformin Start with low dose of OHAs and titrate slowly Adjust dose of medication as renal function deteriorates TREAT the PATIENT and NOT the NUMBERS

Type 2 DM Oral Agents Start with metformin in obese older adult: check renal and hepatic function avoid if Cr Cl below 30 ml/min Start with insulin secretagogue in lean older adult: gliclazide preferred to glyburide gliclazide MR for those who can swallow tablet whole choose repaglinide in those with irregular eating habit and renal impairment CDA Clinical Practice Guideline 2008

Type 2 DM Oral Agents Start with the lowest dose (Half the starting dose) and titrate slowly Starting doses: Gliclazide MR 30 mg daily Repaglinide 0.5 mg od-tid Metfromin 500 mg od

Type 2 DM Oral Agents Second or third line of therapy DPP4 inhibitors (sitagliptin, saxagliptin) Advantage low risk of hypoglycemia Need to have reasonable renal function (egfr >50) α-glucosidase inhibitor (acarbose) Improve post-prandial control Increase GI symptoms Avoid TZD in elderly specially with cardiac history

Insulin in Elderly Basal Insulin once daily Analog basal insulins are associated with less hypoglycemia Lantas or Levemir PreMix insulin bid Novolin 30/70 NovoMix 30 or Humalog Mix 25 Multiple daily injections: Short acting insulin with meals (Humalog, Novorapid, Apidra) Basal insulin at bedtime (Lantus or Levemir)

Three step approach 1>>>> Get Fasting to Target (<9) 2>>>> Get ac meals to Target (7-9) 3>>>> Get pc meals to Target (<14) **>>>> Always eliminate lows (<5)

Pattern Management Watch pattern of BG levels for 2-3 days A pattern consists of BG trend that occurs at the same time of day for at least 2 days Pick problematic areas, address hypoglycemia first then hyperglycemia To correct hyperglycemia, usually aim for fasting levels first, then premeal levels To asses overnight control, check BG at 3:00 am to rule out morning hyperglycemia caused by rebound. CDA: Building competency in diabetes education: advanced practice. 2003:2-41

Sliding scale insulin - bad Sliding scale insulin without a basal insulin is purely REACTIVE and allows for hyperglycemia Not a reliable means of glycemic control in the hospital setting Queale WS. et al. Arch Int Med 1997;157 30

Supplemental scale good! Supplements BASELINE insulin Adjust the baseline insulin or OHA first EXTRA analog bolus insulin ac meals ONLY CORRECTS hyperglycemia Can use supplemental needs to reassess BASELINE doses Adjust BASELINE insulin first before adding supplemental scale!! 31

Plans for Sick Day Management Adjustment of OHAs or insulin at the onset of acute illness If hypreglycemia consider 10-20 % increase in dose of insulin Pay special attention to hydration Adjust CHO intake accordingly Prevent hospitalization

Hypoglycemia Treatment (BG<4) Inform patients of symptoms of hypogylcemia 15-15 rule Glucose tabs (each tablet = 5 g) 15 g of glucose if mild to moderate symptoms. Repeat glucose measurement in 15 minutes Once the blood glucose is within target, the person should have the usual snack or meal, or if this is more than 1 hour away, a snack should be taken:

Hypoglycemia Examine both A1C and CBGM results Assess eating patterns If on insulin secretagogue, reduce dose and/or frequency Assess renal function If on insulin reduce dose by 10-20 percent If on metformin alone, hypoglycemia is rare but possible (over suppression of glucagon) reduce dose and/or frequency

Glycemic Targets Targets: A1C 8.0-8.5% FBG & pre meal BG: 7-9.1 mmol/l pc meals: < 14 mmol/l CBGM bid while adjusting dose

Conclusion In frail elderly with multiple co-morbidities and limited life expectancy there are no evidence to support tight glycemic control Risk of hypoglycemia is increased in this population and could be associated with adverse outcomes Set a appropriate glycemic target to avoid acute complications of DM Additional studies are needed to evaluate higher A1C targets in elderly populations