Oral hypoglycaemic - Treating Type 2

Question 1

Treatment algorithm

Answer 1

Lifestyle modification

Metformin when >6.5% after lifestyle interventions

Metformin + SU/ DPP-4i/ TZD e.g pioglitazone if >7.5% 16 weeks later after metformin and lifestyle

Next if >7.5% after 6 months: triple therapy with metformin, SU + pio/DPP-4i or insulin

Try and achieve less than 7% GLP 1 offered with SU and metformin if high BMI of 35 and triple therapy is not effective, not tolerated or contraindicated or insulin is CI due to occupation, weight loss implications in those <35 BMI

Question 2

Lifestyle: DELAYS

Answer 2

Diet Exercise and education Lipids ABP Aspirin Yearly/ 6 monthly Smoking cessation

Question 3

Metformin

Answer 3

Increases insulin sensitivity, helps lose weight Not metabolised, renally excreted SE: nausea, diarrhoea, abdo pain, lactic acidosis CI: GFR<30, tissue hypoxia (sepsis, MI), morning before GA and iodinated contrast media 500mg BD after food, ↑ing to 2g max.

Question 4

Metformin + SU

Answer 4

SU: increases insulin secretion E.g. gliclazide 40mg ̄c breakfast SE: hypoglycaemia, wt. gain (use glipten if high BMI) CI: omit on morning of surgery

Question 5

Other options to SU

Answer 5

Consider adding a rapid-acting insulin secretagogue (e.g. nateglinide) to metformin instead of a sulfonylurea. May be preferable if erratic lifestyle. Consider adding gliptin to metformin instead of a sulfonylurea if high BMI

Question 6

6 months later >7.5% on metformin and SU, what’s next? Insulin

Answer 6

eg isophane insulin bd or long-acting analogue Add insulin → insulin + metformin + sulfonylurea Contact DVLA - assess fitness to drive if on insulin/ hypo events

Question 7

6 months later >7.5% on metformin and SU, what’s next? Glitazone

Answer 7

Or add glitazone ↑ insulin sensitivity SE: hypoglycaemia, fractures, fluid retention, lft↑ (do lft every 8wks for 1yr, stop if alt up >3-fold). CI: past or present ccf; osteoporosis; monitor weight, and stop if ↑ or oedema if insulin unacceptable Employment, social or recreational issues Obesity metformin + sulfonylurea + sitagliptin / pio (can also replaces metformin/SU)

Question 8

3rd line additional therapy: GLP 1 or DPP-4 inhibitors

Answer 8

GLP 1 analogues: Incretins are gut peptides that work by augmenting insulin release e.g Add exenatide (SC) if insulin unacceptable or BMI>35. Metformin + sulfonylurea + eventide DPP4 inhibitors: prevent 4 breaks down glp-1 sitagliptin: alternative to insulin (if egfr >50), eg if obese (they ↓ appetite)

Question 9

4th line additional therapy

Answer 9

Consider acarbose if unable to use other glucose- lowering drugs ↓breakdown of starch to sugar se: wind (less if slow dose build-up), abdominal distension/pain

Question 10

Actions of GLP 1

Answer 10

Question 11

What are TZD’s?

Answer 11

e.g Rosiglitazone and pio

Pioglitazone is contraindicated by his history of bladder cancer and may contribute to his obesity

PPARγ agonists - transactivation:

Insulin resistance is decreased

Leptin levels decrease (leading to an increased appetite)

TZDs generally decrease triglycerides and increase high-density lipoprotein cholesterol

Question 12

Which oral hypoglycaemic is associated with DKA? What is their action

Answer 12

SGLUT2 e.g Dapagliflozin, canagliflozin & empagliflozin

SGLT2 inhibitors prevent the resorption of glucose from the proximal renal tubule, resulting in more glucose being secreted in the urine.