1 ‘Medicines used in the management of Type 2 Diabetes’ Dr Susan McGeoch, Specialist Registrar in Diabetes Sandra Wilson, Diabetes Specialist Nurse

Introduction 208,279 people with type 2 diabetes in Scotland (SDS 2010) 20,227 people with type 2 diabetes in Grampian (SDS 2010)

Drugs for fixing sugar 1920s : Insulin 1950s : Metformin & Sulphonylureas 1980s : Newer SUs 1990s : Acarbose, Meglitinides 2000s : Glitazones, once daily SUs, Long acting insulin analogues 2007 : Incretin mimetics  Exenatide  Gliptins

4 Types Of Oral Medication Biguanide Sulphonylureas Glitazones Alpha Glucosidase Inhibitor Prandial Glucose Regulators DPP-4 Inhibitors

Injectable medications GLP-1 analogues Insulin 5

Evolution of Type 2 Diabetes Adapted from Bailey CJ et al. Int J Clin Pract 2004; 58: 867–876. Glucose level TIME

Evolution of Type 2 Diabetes Adapted from Bailey CJ et al. Int J Clin Pract 2004; 58: 867–876. Insulin resistance Glucose level TIME

Evolution of Type 2 Diabetes Adapted from Bailey CJ et al. Int J Clin Pract 2004; 58: 867–876. Insulin resistance Insulin production Glucose level Beta-cell dysfunction TIME

9 Local and National Guidelines Grampian Guidelines SIGN NICE BNF

10 Local and National Guidelines Grampian Guidelines SIGN NICE BNF

NICE (CG 87)

12 Biguanides Metformin Reduces insulin resistance and promotes insulin sensitivity 1st Line Choice in the overweight Does Not cause hypoglycaemia GI side effects relatively common Not for use if eGFR <30

13 Sulphonylureas Gliclazide Glipizide Glimepiride Stimulate the pancreas to produce more insulin Can Cause Hypoglycaemia

14 Alpha Glucosidase Inhibitor Acarbose  GI side effects limit use  Slows absorption of carbohydrates  Cannot Cause Hypoglycaemia on its own  Insulin or SU induced hypo in patients taking Acarbose must be treated with glucose (dextrose)

15 Prandial Glucose Regulators Nataglenide (Starlix) Repaglinide (Novonorm) Stimulate insulin production Can cause Hypoglycaemia

16 Glitazones Pioglitazone Promotes insulin sensitivity Contra-indicated in Heart Failure Takes effect in about 6-8 weeks Also available in combination with Metformin (Competact)

THE INCRETIN EFFECT We now know that this is a result of gut secretion GLP-1 and GIP

Glucose orally GLP-1 release INACTIVE GLP-1 DPP4 * * GLP-1 is rapidly degraded by DPP4 enzyme (within minutes) Reduces gastric emptying Reduces acid secretion Increases satiety Reduces appetite Insulin secretion increased Glucagon secretion reduced Preserves B cell function GLP-1R DPP4 inhibitors GLP-1 analogue

19 DPP-4 Inhibitors Sitagliptin (Januvia) reduces blood glucose concentrations by enhancing the effects of ‘incretins’. Incretins are hormones which are produced by the gut in response to food. Vildagliptin (Galvus) Vildagliptin + Metformin (Eucreas) Saxagliptin This drugs are not on the Grampian Formulary

Incretin mimetics GLUCAGON – LIKE PEPTIDE 1 (GLP-1) EXENATIDE (BYETTA)GIVEN BY INJECTION 5 MICROGRAMS TWICE DAILY UP TO 1 HOUR BEFORE FOOD BEST TIME IS WITHIN 15 MINUTES VICTOZA (LIRAGLUTIDE)GIVEN ONCE DAILY AT THE SAME TIME EACH DAY STARTING DOSE OF 0.6MILLIGRAMS FOR 1-2 WEEKS THEN INCREASING TO 1.2 MILLIGRAMS THEREAFTER. GENERALLY USED AS THIRD LINE TREATMENTS IN TYPE 2 DIABETES

Used as 3 rd line therapy. Used on a trial 6 month period having tried other therapies 1 st such as metformin and a sulphonylurea. Tend to be used in people who have type 2 diabetes who are obese with a body mass index of greater than 35 HOW ARE THEY USED?

How do they work They work in 4 ways They only work in response to food They slow gastric emptying They reduce appetite and contribute to weight loss They stimulate insulin secretion and suppress glucagon secretion but only when blood glucose levels are elevated therefore protecting against hypoglycaemia

COMMON SIDE EFFECTS NAUSEA REDUCE APETITE GASTRO INTESTINAL UPSET WEIGHT LOSS NOT RECOMMENDED IN PATIENTS WITH SEVERE GASTROINTESTINAL DISEASE CONTRAINDICATED IN SEVERE RENAL IMPAIRMENT SHOULD NOT BE GIVEN IF eGFR<30 AND SHOULD ALSO NOT BE GIVEN IF THERE IS A PAST HISTORY OF PANCREATITIS

Insulin Profiles

Insulatard Available in prefilled pens (Innolet) Or cartridges (Novopen 4) Or 10ml vial Humulin I Available in prefilled pens (Kwikpen) Or cartridges (Humapen Luxura) Or 10ml vial Taken minutes before a meal Peaks 6-8 hours after injection Lasts between 16 – 20 hours Shake well before administering

Taken once (or twice) daily at the same time to provide 24 hour cover No peak Levemir Available in prefilled pens (Innolet or Flexpen) Or Cartridges (Novopen 4 or Novopen Demi) Lantus Available in prefilled pens (SoloStar) Or cartridges (ClikStar) Or 10ml vial

Taken with meals Peaks 1-2 hours lasts up to 5 hours Novorapid Available in prefilled pen (flexpen) Or cartridges (novopen 4) Humalog Available in prefilled pen (kwikpen) Or cartridges (humapen luxura) Or 10ml vial Apidra Available in prefilled pen (solostar) Or cartridges (clikstar)

Taken 20 – 30 minutes before meal once or twice daily shake well before administration Humulin M3 Available in prefilled pens (Kwikpen) Or cartridges (Humapen Luxura) Or 10ml vial Insuman Comb 15 or 25 or 50 Available in cartridges (Clikstar) Hypurin Porcine 30/70 Available in cartridges (Autopen Classic) Or 10ml Vial

Taken with meals (once, twice or thrice daily) Shake well before administration Novomix 30 Available in prefilled pens (Flexpen) Or Cartridges (Novopen 4) Humalog Mix 25 or 50 Available in prefilled pens (Kwikpen) Or cartridges (Humapen Luxura) Or 10ml vial

30 Sign Guidelines 116 PHARMACOLOGICAL MANAGEMENT OF GLYCAEMIC CONTROL IN PEOPLE WITH TYPE 2 DIABETES REVIEW AND SET GLYCAEMIC TARGET: HBA1C <7% (53 mmol/mol) OR INDIVIDUALISED AS AGREED 1st LINE OPTIONS in addition to lifestyle measures; START ONE OF Metformin (MF) Sulphonylurea* (SU) If intolerant of metformin or If weight loss/osmotic symptoms

31 2nd LINE OPTIONS in addition to lifestyle measures, adherence to medication and dose optimisation; ADD ONE OF Sulphonylurea* (SU) Thiazolidinedione* If hypos a concern (eg driving, occupational hazards, at risk of falls) and If no congestive heart failure DPP-IV inhibitor* If hypos a concern (eg driving, occupational hazards, at risk of falls) If weight gain a concern

32 3rd LINE OPTIONS in addition to lifestyle measures, adherence to medication and dose optimisation; ADD OR SUBSTITUTE WITH ONE OF 3rd line Thiazolidinedione* If no congestive heart failure DPP-IV inhibitor* If weight gain a concern ORAL (continue MF/SU if tolerated) Insulin* (inject before bed) If osmotic symptoms/rising HbA1c; NPH insulin initially If hypos a concern, use basal analogue insulin as an alternative Add prandial insulin with time if required GLP-1 agonists* If BMI >30 kg/m2 If a desire to lose weight Usually <10 years from diagnosis

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