1. Primary Care Prescribing for Type 2 Diabetes Dr. David Jenkins Worcestershire Royal Hospital

2. Outline Evidence for Diabetes Prescribing Glycaemic Targets Treatment Pathways

3. UKPDS

5. UKPDS Metformin

6. UKPDS 5000 patients – 20 years Mean age 54 years Target was fasting glucose Interventions were diet, metformin, SUs and insulin. Mean HbA1c in the intensively treated group was 7% (53 mmol/mol).

7. What has happened since? Explosion in prevalence of diabetes Obesity has dramatically increased Lots of new drugs and insulin formulations Lots of guidelines (and acronyms) A few new trials

8. ACCORD and ADVANCE Investigated very tight glycaemic control 10,000 patients each Aimed for 6% in ACCORD and 6.5% in ADVANCE. Physicians had freedom to intensify treatment as they wished. Less microalbuminuria in ADVANCE More deaths in ACCORD No other statistically significant difference

9. General Conclusions 1) Treating to reduce HbA1c to about 7% with old-fashioned agents reduces complications in a middle-aged UK population. 2) Intensive treatment causes more hypoglycaemia and weight gain. 3) Very intensive treatment may cause more problems than benefits.

10. Principles of treatment Metformin appears to have unique benefits over and above other agents 6 – 8 years of intensive treatment are required to reduce microvascular complications Elderly patients, particularly those with impaired cognition are particularly vulnerable to hypoglycaemia Patients hate weight gain

11. So What Should We Do? Treat patients as individuals Older, frailer patients are less likely to get benefit (and more likely to suffer harm) from intensive treatment Consider the cost-benefits of newer agents in morbid obesity and frail patients Do not use treatments that do not work.

12. Do the new drugs help? Effect on weightReduction in HbA1cCost (per 28 days) PioglitazoneIncrease0.5 – 1%£2 approx. DPP-4 inhibitorsNeutral0.3 – 0.5%£26.60 + GLP-1 inhibitorsDecrease0.5 – 1%£54.14 + SGLT-2Decrease0.5 – 1%£36.59 +

13. Pioglitazone appears to reduce the risk of macrovascular disease. With the exception of Pioglitazone, none of the newer agents have long-term data on safety and benefit. Individually, all have a low risk of hypoglycaemia.

14. Treatment Guideline

15. Insulin in combination with OHAs Reasonable evidence for short and long-term benefit for Metformin - less weight gain; less hypoglycaemia; lower HbA1c compared with biphasic insulin alone. Little long-term evidence for other combinations. Various agents are used for “insulin-sparing”. SGLT-2 inhibitors and GLP-1 inhibitors can limit weight gain.

16. Conclusions The best evidence for long-term treatment for type 2 diabetes comes from the oldest (cheapest and most potent) agents. Treatment and glycaemic targets should be individualised. Intensive treatment does not benefit everyone. Frailty, hypoglycaemia and weight gain will influence the choice of treatment.