Presentation is loading. Please wait.

Presentation is loading. Please wait.

Intensifying glycaemic control in Type 2 diabetics

Similar presentations

Presentation on theme: "Intensifying glycaemic control in Type 2 diabetics"— Presentation transcript:

1 Intensifying glycaemic control in Type 2 diabetics
Dr Miriam Blackburn Staff Specialist The Canberra Hospital

2 Outline Hba1c Targets Guidelines for intensifying glycaemic control
Bariatric surgery Oral hypoglycaemic agents Side effects and PBS listing Starting Byetta Starting Insulin Summary



5 Australian Diabetes Association Guidelines Hba1c target summary
Hba1c goal for most diabetics <7% More intensive targets Women planning pregnancy <6% Requiring lifestyle modification ±metformin Hba1c ≤ 6.0 % Requiring any oral antidiabetic agents other than metformin or insulin Hba1c ≤ 6.5 % ? Risk of hypoglycaemia with sulphonylureas

6 Australian Diabetes Association guidelines for Hba1c targets
Hba1c target of <8% Elderly life expectancy, less than 10 years Advanced cardiac or renal failure CKD stage 4 or 5 NYHA cardiac failure stage 3 or 4 (GFR<30 mls/min) Incurable malignancy Moderate Dementia Hypoglycaemic unaware

7 UKPDS 3867 patients with a new diagnosis (treatment naive) of Type 2 diabetes Randomised to intensive therapy (either metformin, sulphonylurea or insulin) or conventional treatment with diet Mean Hba1c of less than 7% in the first five years of the trial for the intensive group Tight glycaemic control was later lost

8 UKPDS Patients in the intensive treatment group for the first five years Significant reductions in microvascular complications, myocardial infarction and death from any cause Despite loss of the tight control the benefit endured for the next ten years

9 UKPDS Legacy effect 12% reduction in any diabetes related endpoint for patients who had intensive glycaemic control for the first five years

10 The Legacy Effect Are we meeting the Hba1c guidelines?
60% of Australian patients are not meeting Hba1c targets Clinical inertia/patient compliance

11 Case History Mike, a 65 year old Type 2 diabetic
Complicated by mild diabetic retinopathy, no other comorbidities Medications Metformin 2 grams daily Diamicron MR 120 g daily Tried Byetta (unable to tolerate due to nausea) Declining bariatric surgery Hba1c 7.8%, weight 100kg How would you manage this patient?

12 Starting Basal Insulin in a Type 2 Diabetic
Add basal insulin 10 units daily of Protaphane or Lantus Or Add once daily premixed insulin Novomix units with dinner Increase dose by 2-4 units until fasting BSL 4-7 mmol/L 0.2 units per kg/day is a reasonable starting dose for add on basal insulin

13 Guidelines for Intensifying Glycaemic Control


15 Treating a Newly Diagnosed Type 2 Diabetic



18 Intensifying Glycaemic Control for Type 2 Diabetics The traditional way
Step 1 Diet and Exercise Step 2 Metformin Step 3 Metformin plus a sulphonylurea Step 4 Metformin plus a sulphonylurea plus a glitazone Step 4 Insulin

19 Intensifying glycaemic control for Type 2 diabetics A new approach
Step 1 Diet and Exercise plus Metformin Step 2 Dual therapy Metformin plus a Sulphonylurea DPPIV inhibitor plus either a Sulphonylurea or Metformin Byetta and Metformin or a Sulphonylurea Step 3 Triple therapy Consider Byetta plus Metformin and a sulphonylurea Step 4 Insulin +/- oral hypoglycaemic agents

20 Comparing sulphonylureas and DPPIV inhibitors and GLP1 agonists (Byetta)
Cost Cheap Expensive Risk of hypoglycaemia Yes No Effect on weight Weight gain Weight neutral Weight loss Long term safety data and evidence of reduction of microvascular complications GLP1 agonist (Byetta) Cheap Expensive Long term safety data No long term safety data


22 Expected Reduction in Hba1c
DPPIV inhibitors % Byetta 1% Metformin 1-2% Sulphonylurea 1-2% Insulin %

23 Case History Carol, 45 year old Type 2 diabetic Comorbidities
no complications Comorbidities OSA, GORD, OA (waiting TKR) Medications Metformin 2 grams daily, Diamicron MR 120 mg daily, Byetta 10mcg bd s/c, Crestor 20 mg daily, Perindopril plus 5mg/1.25 mg, Amlodipine 5mg, Aspirin 100mg

24 Case History Weight 120kg, BMI 45 Hba1c 9%
Had dietician and exercise physiologist review and lost 4kg in 6/12 then gained 6kg in the next 6/12 What is the next step?

25 Management Refer for bariatric surgery In the meantime, cease Byetta
Continue Metformin and Diamicron and start insulin Novomix units with dinner or Lantus 24 units before bed (based on 0.2 units per kg) Titrate insulin to get before breakfast sugar between 4-7mmol/L


27 Indications for bariatric surgery
Failed weight loss by lifestyle change At least one year of determined effort BMI>40 BMI>35 and severe comorbidities Diabetes, severe osteoarthritis, obstructive sleep apnoea, obesity related cardiomyopathy Motivated and informed Canberra Bariatric holds patient information sessions

28 Gastric Sleeve Tubular stomach, has fewer ghrelin producing cells

29 Gastric Band Purely restrictive procedure

30 Effects of Bariatric Surgery
Mean weight loss 61% Diabetes resolved 77% Hyperlipidaemia improved 70% Hypertension resolved 62% Obstructive sleep apnoea resolved 86% Gastroesophageal reflux symptoms improved Mortality due to operative complications less than 1%, adverse events 20% 30% reduction in mortality due to a reduction in the comorbidities (less cancer, IHD and diabetes related deaths)

31 Complications of Gastric Banding
Restrictive procedure Easily reversible Lowest mortality rate of all bariatric procedures (0.05%) High rate of revision surgery required (40-50%) Complications Acute stomal infection, band infection, haemorrhage, pulmonary emboli, band erosion, band slippage, prolapse or tubing malfunction

32 Complications of Sleeve Gastrectomy
Lower rate of complications than gastric bypass Mortality 0.39% Common complications (3-24%) Bleeding Narrowing or stenosis of gastric stoma Gastric leaks Reflux

33 Costs of Bariatric Surgery
If patient has private health insurance $6000-$7000 out of pocket If patient has no private health insurance $ Public funding coming soon…. Limited number Strict criteria for eligibility

34 Case History Jan, 45 year old Type 2 diabetes Diabetes for 10 years
Insulin for 4 years No complications Medications Metformin 2 grams daily Diamicron MR 120 mg daily Lantus 30 units nocte

35 Case History Hba1c 8% Fasting sugar readings 5-6 mmol/L
Weight 98 kg, BMI 33 How would you treat this patient?

36 Management of a Type 2 Diabetic not meeting Hba1c targets on Basal Insulin
Stop Diamicron Stop sulphonylureas when short acting insulin started Continue Metformin To assist with prevention of insulin associated weight gain Start twice daily pre-mixed insulin Novomix units morning and 10 units at night

37 Mechanism of action Side effects PBS criteria
Antihyperglycaemic Agents Mechanism of action Side effects PBS criteria

38 Thiazolidinediones Rosiglitazone (Avandia) and Pioglitazone (Actos)
Side effects Weight gain Congestive cardiac failure Osteoporosis and fractures Rosiglitazone (Avandia) Boxed warning Increased risk myocardial infarction and congestive cardiac failure Adverse effect on lipids Pioglitazone (Actos) Increased risk of bladder cancer

39 Acarbose (Glucobay) Inhibit upper gastrointestinal enzymes
(alphaglucosidases) and slow the absorption of carbohydrate Side effects 73% flatulence Diarrhoea Compliance maybe poor due to side effects

40 DPPIV inhibitors SITAGLIPTIN (Januvia) Saxagliptin (Onglyza) Linagliptin (Trajenta) Vildagliptin (GALVUS)

41 How do DPPIV Inhibitors Work? The Incretin Effect
An oral dose of glucose causes more insulin secretion than the same dose given intravenously Glucose in the gut stimulates release of incretins (Glucagon like peptide 1, GLP1 and gastric inhibitory polypeptide, GIP) which increase insulin secretion Patients with diabetes produce less incretins

42 How do DPPIV inhibitors work?
Dipeptidyl peptidase 4 (DPPIV) is an enzyme which metabolises incretins DPPIV inhibitors inhibit DPPIV and cause higher incretin levels This increases insulin secretion and lowers glucose levels Glucose dependant increase in incretin levels therefore no risk of hypoglycaemia (when used as a single agent or with Metformin)

43 Action of DPPIV inhibitors

44 DPPIV Inhibitors Modest effect on Hba1c approximately 0.5% reduction
Agents within this drug class have similar efficacy No long term safety data Expensive Weight neutral No risk of hypoglycaemia (unless combined with agents that cause hypoglycaemia e.g. sulphonylurea)

45 Side effects of DPPIV Inhibitors
Well tolerated Immune function Small increased risk of nasopharyngitis, urinary tract infections and headache Slight increased risk of gastrointestinal side effects with sitagliptin Linagliptin rare reports of LFT abnormalities (monitor LFT 3/12) Reports of hypersensitivity reactions Anaphylaxis, angioedema, Stephen Johnsons syndrome Pancreatitis case reports Avoid using if history of pancreatitis or risk factors for pancreatitis (gallstones, severe hypertriglyceridaemia or alcoholism) Consider pancreatitis if severe abdominal pain develops

46 Incretin Associated Pancreatitis
Retrospective analysis Incidence of acute pancreatitis Control group Type 2 diabetics not on (DPPIV inhibitors or GLP1 agonists) 2.7 per thousand developed pancreatitis Type 2 diabetics taking DPPIV inhibitors or GLP1 agonists 4.1 per thousand developed pancreatitis

47 Incretin Associated Pancreatitis
Type 2 diabetes increase the risk of pancreatitis two fold Acute pancreatitis increases the risk of pancreatic cancer ?Incretin associated pancreatitis increase the risk of pancreatic cancer Need large scale prospective randomised controlled trials to clarify these questions

48 PBS requirements for DPPIV inhibitors Linagliptin, Sitagliptin, Vildagliptin and Saxagliptin
Streamlined authority Dual oral combination therapy with metformin or a sulfonylurea and Hba1c>7% Type 2 diabetes where a combination of metformin and a sulfonylurea is contraindicated or not tolerated and Hba1c>7%

49 PBS requirements for DPPIV inhibitors
Private script if used as a single agent Private script if used as triple therapy with Metformin and Sulphonylurea Not to be used with insulin

50 Comparing DPPIV inhibitors
Linagliptin (Trajenta) Once daily, one dose 5mg No dose adjustment required in renal impairment Saxagliptin (Onglyza) Once daily 2.5 mg and 5 mg Cease if eGFR<60mls/min Sitagliptin (Januvia) Twice daily Dose adjust with renal impairment Janumet (combination with Metformin) Vildagliptin (Galvus) Once or twice daily Cease if moderate renal impairment Galvumet (combination with Metformin)

51 Sitagliptin (Januvia) dosing and renal impairment
Creatinine clearance >/= 50 ml/min 100mg once daily Creatinine clearance >/=30 and less than 50 ml/min 50mg daily Creatinine clearance <30 ml/min 25mg daily

52 Case History Cindy is 45 year old Type 2 diabetes for 4 years BMI 30
No complications Medications Metformin XR 2 grams daily Gliclazide MR 120 mg daily Hba1c 7.4 %

53 Management How would you treat this patient?

54 Management Discuss with patient Add Byetta (halve gliclazide dose)
Or add once daily insulin (options Lantus/Novomix 30/Protaphane) The advantage of Byetta is possible weight loss compared with likely weight gain with insulin

55 Exenatide (byetta) LiRagluTIDe (VICTOZA)
GLP1 Agonists Exenatide (byetta) LiRagluTIDe (VICTOZA)

56 How GLP1 Agonists work Bind to GLP1 receptor
Glucose dependant increase insulin secretion in response to food Slows gastric emptying and suppresses appetite Suppresses inappropriately high glucagon levels Weight loss

57 Side Effects of GLP 1 Agonists
Main side effects gastrointestinal Nausea, vomiting and diarrhoea Nausea usually wanes after a few weeks Weight loss 1.44 kg Hypoglycaemia only if combined with a sulphonylurea Case reports of pancreatitis ?causal Avoid using if history of pancreatitis or risk factors for pancreatitis (gallstones, severe hypertriglyceridaemia or alcoholism) Consider pancreatitis if severe abdominal pain develops

58 Side effects of GLP1 agonists
Case reports of acute renal failure Contraindicated if creatinine clearance <30mls/min Monitor EUC if creatinine clearance mls/min Check one week after starting Byetta and one week after increasing the dose to 10mcg

59 PBS requirements for Byetta
Streamlined authority Dual combination therapy with metformin or a sulfonylurea and Hba1c >7% “where a combination of metformin and a sulfonylurea is contraindicated or not tolerated” Triple combination therapy with metformin and a sulphonylurea and Hb1ac >7%

60 Starting Byetta Start with Byetta 5mcg BD s/c
In combination with Metformin, a Sulphonylurea or both After 30 days the Byetta 5mcg pen will be finished start the Byetta 10mcg pen Reduce Sulphonylurea if concerned about hypoglycaemia

61 Starting Byetta Never use in Type 1 diabetics
If already on insulin do not stop insulin and start Byetta Warn the patient about nausea, which usually settles down after the first few weeks If vomiting seek medical advice (risk of acute renal failure)

62 Exenatide (Byetta) What to tell the patient
Injections are twice daily within one hour of morning and evening meals Avoid extremes of temperature Less than 25 degrees, pen being used doesn’t need to be in the fridge “If you are comfortable so is the Byetta” Keep unused pens in the fridge Needles are free from the NDSS Reduce meal size to reduce nausea

63 Diabetes Educators to assist with Byetta starts
Byetta helpline: The Canberra Hospital Byetta start group Ph: Fax: Diabetes ACT (Holder) Ph: Community Centres (Gungahlin, Belconnen) Private Diabetes Educator (Simon Scott-Findlay)

64 Liraglutide (Victoza)
TGA approved not PBS listed Once daily injection (0.6mg. 1.2mg, 1.8mg) Weight loss 3kg May have larger decrease in Hba1c than Exenatide Side effects nausea, vomiting and diarrhoea (10-40%)

65 Liraglutide (Victoza)
Minor hypoglycaemia Increased Medullary thyroid cancer in rats Thought to be species specific Expression of GLP1 receptor in C-cells is low Humans have fewer C-cells than rats Contraindicated if creatinine clearance <30mls/min or hepatic impairment

66 Costs for Private Scripts
Victoza $ $ (depending on the dose) for 2 pens Sitagliptin $90 for 28 tabs Byetta $175 per month

67 Case History Marcia is a 40 year old woman who presents with polyuria, polydipsia and fatigue No ketonuria Her father has Type 2 diabetes BMI 32 Random BSL 28 mmol/L, Hba1c 12% How would you treat this patient?

68 Treatment of a Newly Diagnosed Symptomatic Type 2 Diabetic
Diet and exercise Start Byetta (in combination with two oral hypoglycaemic agents) or insulin (Novomix units twice daily) to give symptom relief, once glucose toxicity resolves may be able to change to dual oral agents Diabetic eye review – warn about blurred vision, don’t get glasses prescription changed for at least 6 weeks

69 Case History Greg is 33 years old
Type 2 Diabetes diagnosed 6 months ago BMI 27 Current treatment Diet, Exercise and Metformin 2 grams daily Now Hba1c 7.1 % How would you treat this patient?

70 Treatment Add a DPPIV inhibitor or Byetta to achieve an Hba1c <6.5%
Risk of hypoglycaemia with a sulphonylurea What would have been the best option if his Hba1c was 8%?

71 Case History Hba1c 6.3% Bobby is a 70 year old male
Type 2 diabetes for 12 years Ischaemic heart disease (CABG) Ischaemic cardiomyopathy (NYHA IV) Peripheral vascular disease Chronic renal failure (eGFR 42 mls/min) Medications (only diabetes related medications are listed) Metformin 3 grams daily Amaryl (Glimepiride) 2mg daily Hba1c 6.3%

72 Management What is your Hba1c target?
How does his renal impairment affect your management?

73 Management Hba1c target 7 - 8% Metformin and renal failure
(long duration of diabetes, age, ischaemic heart disease/CCF) Metformin and renal failure NICE (UK) guidelines Stop Metformin if eGFR < 30 mls/min Reduce dose if eGFR < 45 mls/min

74 Management Low dose Metformin 1 gram daily Stop sulphonylurea
Hba1c too low Risk of hypoglycaemia Could add in Linagliptin if blood sugar levels too high on low dose Metformin

75 Case History Peter is a 45 year old
Presents with diabetes for 6 months No family history of diabetes Current treatment Metformin BMI 20 Hba1c 9% How would you treat this patient?

76 Type 1.5 Diabetes Latent Autoimmune Diabetes in Adults (LADA)
Stop Metformin Start basal bolus insulin Lantus 10 units daily Novorapid 3 units tds

77 Type 1.5 Diabetes Latent Autoimmune Diabetes in Adults (LADA)
Diagnostic clues Less than 50 years of age BMI<25 Personal or family history of autoimmune disease No family history of Type 2 diabetes Weight loss or ketones

78 Type 1.5 Diabetes Latent Autoimmune Diabetes in Adults (LADA)
Endocrinologist review Confirm the diagnosis IA2 antibodies GAD antibodies C-peptide Treatment Basal bolus insulin

79 Insulin Commencement

80 Duration of action of different insulins

81 Progressing insulin therapy if not meeting Hba1c targets
Basal insulin Lantus or protaphane or Novomix 30 once daily BD insulin (two prandial injections) Novomix 30, Mixtard 30 Lantus or protaphane plus Novorapid or Actrapid Basal bolus (three prandial injections) Once daily Lantus or protaphane plus Novorapid or Actrapid three times per day with meals

82 Starting Basal Insulin in a Type 2 Diabetic
Starting dose 10 units or 0.2 units per kg Check fasting BSL increase insulin every 3 days by 2-4 units until fasting BSL between 4-7mmol/L Hypoglycaemia reduce by 4 units or 10%

83 Starting Basal Insulin in a Type 2 diabetic
Starting doses units/kg/day If markedly hyperglycaemic units/kg/day Typical insulin doses (after titration) for type 2 diabetics are between units per day (0.5-1 unit/kg/day) Add nocte basal insulin to current oral hypoglycaemic therapy

84 Starting Basal Insulin in a Type 2 Diabetic
Basal insulin options Protaphane, Lantus, Novomix 30 (a mixture of protaphane and Novorapid) taken with dinner The need for prandial insulin is more likely when the daily dose of basal insulin exceeds 0.5 units/kg/day, particularly if >1 unit/kg/day

85 How can you predict insulin requirements?
Very high sugar readings initially likely to need higher doses of insulin due to glucose toxicity Insulin resistance is proportional to weight Thin patients will need small doses of insulin Obese patients will need higher doses Older frail patients start low go slow

86 Reasons people refuse insulin
Fear of needles Show them the device Show them a 4mm needle, explain it hurts less than finger pricking Diabetes educator review A “trial” of insulin If phobia is severe  diabetes psychologist

87 Reasons People Refuse Insulin
Feeling of failure “I should have been able to manage this with diet and exercise alone” Explain that diabetes is a progressive disorder and most diabetics will end up on insulin eventually Fear of weight gain 2kg per year Use insulin in combination with Metformin to try to limit insulin associated weight gain

88 Natural History of Type 2 Diabetes

89 Case History Alice is an 80 year old woman Type 2 diabetes Severe COPD
No complications, eGFR 60 mls/min Medications Metformin 2 grams daily Diamicron MR 120 mg daily Hba1c 10% BMI 19, weight 48 kgs How would you treat this patient?

90 Treatment of an Elderly Type 2 Diabetic Requiring Insulin
Elderly, thin Start basal insulin (Lantus, protaphane) or once daily Novomix 30 in addition to oral agents 8 units per day Start low go slow! Or Stop oral agents Start Novomix 30 8 units with breakfast and dinner

91 Case History Bobby is a 55 year old Type 2 Diabetic
Hba1c 8 %, weight 98kg, fasting BSL average10 mmol/L Medications Lantus 30 units nocte Metformin 2 grams daily Diamicron MR 120 mg daily How would you treat this patient?

92 Management Increase Lantus dose by 4 units every 3 days until fasting blood sugar less than 7 mmol/L If next Hba1c not to target Stop Lantus and Diamicron and start Novomix units breakfast and 10 units dinner, continue Metformin

93 Summary Aim for aggressive glycaemic control early in the disease (avoiding hypoglycaemia) Less aggressive glycaemic control if elderly, hypoglycaemic unaware, end stage congestive cardiac failure or chronic renal failure

94 Summary Intensifying glycaemic control in Type 2 diabetics
If BMI> 35 consider bariatric surgery If BMI less than 35 Step 1: Monotherapy Metformin Step 2: Dual Therapy Add in DPPIV inhibitor, Sulphonylurea or Byetta Step 3: Triple therapy Consider Byetta with Metformin and Sulphonylurea Step 4: Insulin Insulin Basal insulin BD insulin Basal Bolus

95 The End

96 Sodium glucose cotransport 2 inhibitors
SGLT2 sodium dependant glucose transporter Dapagliflozin blocks SGLT2 and prevents reabsorption of glucose Glucosuria  calorie loss in the urine  weight loss

97 Recent TGA listing Bydureon (once weekly exenatide)
Company not selling this privately in Australia Byetta has been TGA approved in combination with Metformin and basal insulin

Download ppt "Intensifying glycaemic control in Type 2 diabetics"

Similar presentations

Ads by Google