How can we improve outcomes in Type 2 diabetes? Earlier diagnosis Better patient education Stress central role of lifestyle management Identify and treat all risk factors Use rational pharmacological therapy in treating hyperglycaemia
Treating Type 2 diabetes -Traditional approach Diagnosis made opportunistically or when patient presents with symptoms Lifestyle management and patient education Add oral therapies and or newer agents Add insulin However treatments are changing
Lifestyle Interventions Refer for dietary review Offer DSESMOND structured education programme Re Check HbA1c in 3-6months No improvement ( HbA1c >48mmol/mol)
DESMOND An example of structured education in Type 2 diabetes: Diabetes Education and Self Management for Ongoing and Newly Diagnosed Type 2 diabetes Meets the criteria set out by NICE (2003) but is not suitable for non-english speaking participants (DESMOND BME is in development)
Oral Hypoglycaemic agents Consider renal, hepatic impairment, age of patient, hypoglycaemia risk, and weight gain First Line Consider Biguanide, Metformin (Glucophage) 500mg initially (max. dose 2g daily) Titrate dose on a weekly basis to reduce side effects (If not able to tolerate standard release Metformin, consider Metformin MR) (Use with caution in renal impairment egfr <45 review and avoid if <30 risk of Lactic Acidosis) Repaglinide 500micrograms-4mg tablets max. dose 16mg per day -can be considered if Metformin contra indicated or not tolerated, (However, there is no licensed non-metformin-based combination containing Repaglinide that can be offered at first intensification)
DPP-IV inhibitors (Gliptins) DPP-4 inhibitor (Dipeptide peptidase-4 inhibitor) GLIPTINS Linagliptin (Trajenta) 5mg daily (no renal cautions) Sitagliptin (Januvia) 100mg daily (Caution in renal impairment) Others that can be considered: Saxagliptin (Onglyza) 5mg daily (Cautions in renal and hepatic impairment) Vidagliptin (Galvus) 50mg twice daily (Monitor liver function, caution in renal impairment
SGLT-2 (Sodium-glucose cotransporter 2 inhibitors) Canagliflozin 100mg-300mg daily before breakfast (avoid if EGFR <60) Dapagliflozin (Forxiga) 10mg daily (avoid if egfr<60) Empagliflozin (Jardiance) 10mg/25mg daily (avoid if egfr<60) All available in combination with Metformin
SGLT-2 IMPORTANT SAFETY INFORMATION RISK OF DIABETIC KETOACIDOSIS (DKA) Potential life threatening cases of DKA have been reported in patients taking SGLT-2 inhibitors To minimise the risks: Advise patient how to recognise signs & symptoms of DKA such as nausea, abdominal pain, excessive thirst, difficulty in breathing, fatigue, sleepiness and to seek prompt medical attention if symptoms develop Test for ketones if patient presents with symptoms (could have near normal blood glucose levels)
GLP-1 Agents (Glucagon Like peptide-1) weekly injections Dulaglutide (Trulicity) (avoid if egfr <30) 0.75mg as monotherapy or 1.5mg as add on therapy with other glucose lowering agents or insulin, once weekly injection or Exenatide MR (Bydureon) (avoid if egfr<50) 2mg once weekly injections in combination with other Glucose lowering agents or basal insulin
Daily GLP-1 agents Liraglutide (Victoza) (6mg/1ml) pre filled pen device dose 0.6mg/ 1.2mg/ 1.8mg (avoid if egfr <30, see hepatic cautions) Daily injection Lixisenatide (Lyxumia) (50mcg/1ml) pre filled pen device 10mcg for 2 weeks then 20mcg Daily injection (Avoid if egfr <30, no hepatic caution) Can be used in combination with oral glucose agents and basal insulins
Points to consider... All GLP-1 agents contraindicated in gastro-intestinal disease and if previous history of pancreatitis Patients should be counselled about potential side effects prior to starting GLP-1 agents. NICE recommend discontinuing GLP-1 after 6 months if HbA1c not improved by 1% and/ or weight loss of at least 3%
Sulphonylurea (SU) Gliclazide (Diamicron) 40mg-80mg daily adjusted according to response every 4 weeks (after 2 weeks if no decrease in blood glucose) Can be increased to twice daily (Gliclazide MR also available) Can be used in renal impairment but monitor blood glucose Others that can be considered: Not used routinely at present Glibenclamide 5mg daily Glimepiride 1mg-4mg daily Glipizide 2.5-5mg daily (avoid if both renal & hepatic impairment) Tolbutamide 0.5-1.5mg daily (can be use in renal impairment as short acting but must be monitored)
Pioglitazone (thiazolidinedione) Pioglitazone (Actos) 15mg/ 30mg/45mg tablets one daily adjusted according to response. (also available in combination with Metformin) IMPORTANT SAFETY INFORMATION Increased incidence of heart failure when combined with insulin especially in those with predisposing factors e.g. previous MI. Should be closely monitored foe signs of heart failure, should not be used in patients with history of heart failure
Safety Information cont Small increased risk bladder cancer however if patient responding to treatment benefits outweigh the risks Should not be used in patients with previous history of bladder cancer Before initiating patients should be assessed for risk factors of bladder cancer Patients should be reviewed after 3-6 months if no response to treatment it Pioglitazone should be stopped
The stepwise treatment of Type 2 diabetes Healthy eating and exercise - HbA1c 48mmol/mol (6.5%) + Structured Education + Metformin First Intensification- if HbA1c rises to 58mmol/mol (7.5%) Consider adding a DPP-4i/ Pioglitazone/ SGLT-2/ Sulphonylurea NICE Guideline NG28, updated April 2017
Continued Second Intensification- if HbA1c rises to 58mmol/mol (7.5%) Consider Triple therapy with: Metformin, Dpp-4i and Sulphonylurea(SU) Metformin Pioglitazone and SU Metformin, Pioglitazone or an SU and an SGLT-2
If not tolerated or effective Consider Combination therapy: Adding GLP-1 mimetic for adult patients with BMI of 35kg/m² or higher Or Have a BMI lower than 35m² for whom insulin would have significant occupational implications or weight loss would be benefit other significant obesityrelated comorbidities NICE Guideline NG28, updated April 2017
So. Many different glucose lowering agents available - one type does not fit all! Optimal blood glucose control is not always obtained due to limitations and action of the medication and factors which affect blood glucose control Remember timing of oral medications can be important Newer treatment and combinations are being developed