Mission Possible: Pharmacology made easy- Diabetes in ARRC edition

1. Mission Possible: Pharmacology made easy- Diabetes in ARRC edition Sara Salman Clinical Advisory Pharmacist Health Hawkes Bay

2. What’s the difference from other Diabetes

3. Treatment goals • Glycaemic target 54-70 • Avoiding hypoglycaemia • CV risk factor management • Smoking cessation • Treatment of hypertension • Treatment of dyslipidaemia • Aspirin therapy • Exercise

4. Aspirin therapy in DM • Daily aspirin in patients with macrovascular dx is widely accepted (secondary prevention). • A meta-analysis of a large number of secondary prevention found that absolute benefit of aspirin was greatest in over 65yrs with diabetes or diastolic hypertension. • The role of aspirin for primary prevention of CV in patients with diabetes is less certain.

5. Pathophysiologyin T2DM

9. Metformin • Metformin is 1st line for all people with T2DM • Also prescribed to people with pre-diabetes • Evidence may provide CV protection beyond reducing HbA1c • Actions • Decreases glucose formation in liver • Increases peripheral utilisation of glucose

10. Metformin Adverse Effects • Nausea • Vomiting • Anorexia • Diarrhoea • Malabsorption of vitamin B12 • Rash – infrequent • Lactic acidosis – rare, but often fatal- avoidance in SICK days

11. Lactic acidosis • Risk factors • renal impairment • old age (reduced renal function) • high doses of metformin (> 2 gram/day) • Discontinue metformin temporarily: • Prior to surgery • Prior and after use of IV contrast media • Illness causing dehydration e.g. vomiting, diarrhoea

12. Vitamin B12 deficiency • 30% patients • May present without anemia and as a peripheral neuropathy • it is often misdiagnosed as diabetic neuropathy •  Progression of central and/or peripheral neuronal damage can be arrested but not reversed with vitamin B12 replacement

13. Sulfonylurea • Actions • Increasing insulin secretion from functional pancreatic beta-cells • Often added to metformin when HbA1c target not achieved • 3 fully-subsidised in NZ • Glipizide • Gliclazide • Glibenclamide

14. Sulfonylureas

15. Sulfonylurea Adverse Effects • Weight gain • Hypoglycaemia • Risk increased by advanced age, renal or hepatic impairment • Nausea, diarrhoea, metallic taste, headache, rash – infrequent • Blood disorders, allergic reaction, photosensitivity, hepatotoxicity - rare

17. Sulfonylurea advise • Take with food to minimise hypoglycaemia risk • Drinking alcohol (advise for all patients with diabetes) • May mask hypoglycaemia symptoms • Avoid binge drinking • Eat when drinking alcohol • Know how to recognise and treat hypoglycaemia

18. Pioglitazone (Glitazone) • Actions • ‘Insulin sensitiser’ (like metformin) • Increases body’s ability to transport glucose across cell membrane • Peroxisome proliferator-activated receptor gamma (PPAR-ɣ) agonist which regulates genes involved in lipid and glucose metabolism • Increases sensitivity of peripheral tissues to insulin • Decreases hepatic glucose output

19. Pioglitazone Adverse Effects • Peripheral oedema & fluid retention • Weight gain (worse with insulin combination) • Headache, dizziness • Nausea/vomiting • Arthralgia • Decrease in haemoglobin and haematocrit • Fractures – infrequent • Elevated LFTs, hepatocellular injury, heart failure, pulmonary oedema, macular oedema - rare

20. Pioglitazone • What to watch out for? • Swollen feet or ankles • Breathlessness • Fatigue • Loss of appetite • Dark urine • Refer to prescriber if family or personal history of bladder cancer

21. Pioglitazone Practice Points • If not effective/ if achieved 5 mmol/mol reduction in HbA1c after 6 months is not achieved • Monitoring liver enzymes • Baseline & every 2 months for 1st year, then periodically • Symptoms of liver toxicity – nausea, abdominal pain, dark urine or jaundice = discontinue tx. • Limited long term safety data • Stop if heart failure diagnosed

22. Alpha glucosidase inhibitors- Acarbose • Actions • Delays intestinal absorption of CHO by inhibiting alpha-glucosidase enzymes in small intestine • Enzyme which breaks down complex CHO into glucose • Reduced postprandial hyperglycaemia • Little effect on fasting glucose levels

23. Acarbose adverse effects • Flatulence (75% patients affected) • Diarrhoea (or soft stools) • Abdominal pain and distention • Increased aminotransferase concentrations – infrequent (monitor monthly for 1st 6 months) • Ileus, hepatotoxicity, skin reactions, anaemia – rare NOTE: no risk of hypoglycaemia as monotherapy

24. Acarbose is avoided in: • Contraindicated in patients with (or risk of) • Partial intestinal obstruction • Inflammatory bowel disease • Major hernia • GI disorders with malabsorption • Avoid use if CrCl<25mL/min • Hypoglycaemia (combination treatment) • Treatment: glucose NOT sucrose e.g. glucose tablets not jellybeans

25. Acarbose Practice Points • Swallow whole • Take with liquid immediately before a meal or with first mouthfuls of food • GI adverse effects • Dose dependent(200mg tds maximum dose) • Increased by taking sucrose • Reduced by starting on low dose and slow titration(e.g. 50mg tds after 4-8 weeks 100mg tds) • Improves as treatment continues • Unlikely to be alleviated by antacids

26. Summary • Selection based on individual patient, treatment goals and risks.

27. Basal vs Bolus

28. Examples

30. Which Tom has diabetes?

31. Questions?

33. Gliptins- DDP4 (Dipeptidyl Peptidase-4 inhibitors) • Dipeptidyl peptidase 4 (DPP-4) inhibitors (DPP-4i) increase endogenous incretin levels by blocking the action of DPP-4 • Once-a-day oral agents with no risk of hypoglycemia • Weight-neutral, when used as monotherapy, and therefore may be attractive agents to use in older adults. • Since they are relatively weak agents and usually lower A1C levels by only 0.6 percent, DPP-4 inhibitors should only be used as monotherapy when the A1C level is relatively close to the goal level.

34. Flozins- SGLT2 inhibitors • Sodium–glucose co-transporter 2 (SGLT-2) inhibitors. • SGLT-2i reduce renal glucose reabsorption

35. Extra slides

36. Extra slides