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What Next After Metformin Latest Evidence and Guidelines Weds 14 July 2021 @Lwnurses #LWN #LearnWithNurses Judy Downey RGN BSc hons Independent Diabetes Nurse Consultant Associate Trainer Education for Health Associate Lecturer New South Bucks University Author Practice Nurse Journal Former Committee Member Primary Care Diabetes Society @DowneyJude2757 Different modes of action by diabetes therapies • Reducing insulin resistance - TZD • Stimulating insulin production in the pancreas - SUs • Delaying carbohydrate digestion - Acarbose • Incretin enhancers – DPP4i • Incretin mimetics – GLP analoguess • Blocking the reuptake of glucose from the kidneys – SGLT2i • Prevent liver converting fats to glucose, and enable cells to respond more effectively to insulin – Metformin. FIRST LINE. Glycaemic control • How important is it? • Is it as important for all patient groups? • What’s the legacy effect? • What is ‘good’ control? NICE Guidance 1. NICE guidelines NG28 (issued December 2015, updatedApril 2017): Type 2 diabetes in adults: management. https://www.nice.org.uk/guidance/ng28.Last accessed January 2018The Science behind the Guidance Cardiovascular Outcome Trials or CVOTs Key findings from these landmark studies demonstrated reductions in major adverse cardiovascular events (MACE; cardiovascular death, non-fatal myocardial infarction or stroke) in the EMPA-REG OUTCOME (Empagliflozin) and CANVAS (Canagliflozin) programmes, and the reduction in the co-primary endpoint of hospitalisation for heart failure (HHF) and cardiovascular death in the DECLARE-TIMI 58 trial (Dapagliflozin), as well as the significant reduction in HHF in all three trials.The Science behind the Guidance Cardiovascular Outcome Trials or CVOTs The CREDENCE (Canagliflozin) trial in those with type 2 diabetes at high risk of cardiovascular and renal events demonstrated a significant reduction in the combined renal outcome, resulting in a licence change in July 20 for canagliflozin to treat DKD in those living with type 2 diabetes. DAPA-CKD, a renal outcome study similar to CREDENCE with dapagliflozin, reduced major adverse renal events in those with and without type 2 diabetes, and a licence change is currently awaited.The Science behind the Guidance Cardiovascular Outcome Trials or CVOTs The DAPA-HF study demonstrated significant reductions in a combination of worsening HF and cardiovascular death in those with and without type 2 diabetes, with reductions in both cardiovascular and all-cause mortality. This resulted in a licence change for dapagliflozin in November 2020 allowing use in those with HF and reduced ejection fraction (HFrEF; ejection fraction ≤40%) in adults with or without type 2 diabetes. Finally, the EMPEROR-Reduced trial (Empagliflozin) in those with HFrEF with and without type 2 diabetes demonstrated reductions in cardiovascular death and HHF in those treated with empagliflozin. A UK licence change is awaited. Glucose-lowering medication in type 2 diabetes: overall approach. Melanie J. Davies et al. Dia Care 2018;41:2669-2701 ©2018 by American Diabetes Association Choosing glucose-lowering medication if compelling need to minimize hypoglycemia. Melanie J. Davies et al. Dia Care 2018;41:2669-2701 ©2018 by American Diabetes Association Melanie J. Davies et al. Dia Care 2018;41:2669-2701 ©2018 by American Diabetes AssociationMr C Age (years): 52 BMI (kg/m ): 29 Type 2 diabetes Newly diagnosed diagnosed: HbA 1c 68 mmol/mol (8.4%) Diabetes medication: N/A eGFR (ml/min): 90 Lipids (mmol/L): TC 4.8 LDL 3.0 TG 2.2 HDL 1.0 Blood pressure (mmHg): 158/88 Ethnicity: SouthAsian Lifestyle: Smokes 10/day; 20 units alcohol/week; eats out regularly Occupation: Accountant ADA/EASD position statement: Intensiveness of glucose lowering should be individualised Patient/disease features More stringent HbA 1c 7% Less stringent Risks potentially associated with hypoglycaemia Low High Disease duration Newly diagnosed Long-standing Usually not Life expectancy modifiable Long Short Important comorbidities Absent Few/mild Severe Established vascular complications Absent Few/mild Severe Patient attitude and Highly motivated, adherent, Less motivated, Potentially expected treatment efforts Excellent self-care capacitieson-adherent, poor self-care modifiable capacities Resources and support system Readily available Limited ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes. Inzucchi SE et al (2015) Diabetes Care 38: 140–9 ADA/EASD position statement: Intensiveness of glucose lowering should be individualised Patient/disease features More stringent HbA 1c 7% Less stringent Risks potentially associated with hypoglycaemia Low High Disease duration Newly diagnosed Long-standing Usually not Life expectancy modifiable Long Short Important comorbidities Absent Few/mild Severe Established vascular complications Absent Few/mild Severe Patient attitude and Highly motivated, adherent, Less motivated, Potentially expected treatment efforts Excellent self-care capacitieson-adherent, poor self-care modifiable capacities Resources and support system Readily available Limited ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes. Inzucchi SE et al (2015) Diabetes Care 38: 140–9 Mr C 6 months later Age (years): 52 BMI (kg/m ): 29 Type 2 diabetes diagnosed: 6 months HbA : 68 62 mmol/mol (7.8%) 1c Diabetes medication: Metformin 1000 mg bd eGFR (ml/min): 90 Lipids (mmol/L): TC LDL TG 1.8 Atorvastatin 4.0 HDL 1.2 2.7 20mg OD Blood pressure (mmHg): 129/82 Lisinopril 10mg Ethnicity: SouthAsian Lifestyle: Smokes 10/day; 20 units alcohol/week; eats out regularly Occupation: AccountantVoting question: What would you suggest? 1. Add a Sulphonylurea? 2. Add a DPP-4 inhibitor? 3. Add Pioglitazone? 4. Add an SGLT2 inhibitor? 5. Add a GLP-1 receptor agonist? 6. Add Insulin? Mr 6 months later C Age (years): 53 BMI (kg/m ): 29 26 Type 2 diabetes 12 months diagnosed: HbA 1c 62 mmol/mol 54 mmol/mol (7.1%) Diabetes medication: Metformin 1000 mg bd; Canagliflozin 300mg OD eGFR (ml/min): 85 Lipids (mmol/L): TC 4.0 HDL 1.2 LDL 2.7 TG 1.8 Blood pressure 125/80 (mmHg): Lifestyle: Smokes 10/day; 20 units alcohol/week; eats out regularly Occupation: AccountantVoting question: What would you suggest? 1. Review in 6 months? 2. Add a DPP-4 inhibitor? 3. Add pioglitazone? 4. Add insulin? 5. Add a GLP-1 receptor agonist? 6. Add a sulphonylurea? Mr C 1 year later Age (years): 54 2 BMI (kg/m ): 26 30 Type 2 diabetes 2 years diagnosed: HbA : 54 63 mmol/mol (7.9%) 1c Diabetes medication: Metformin 1000mg BD; Canagliflozin 300mg OD eGFR(ml/min): 80 Lipids (mmol/L): TC 4.8 HDL LDL 3.0 TG 2.2 1.0 Blood pressure (mmHg): 130/85 Ethnicity: SouthAsian Lifestyle: Smokes 10/day; 20 units alcohol/week; eats out regularly Occupation: AccountantVoting question: What would you suggest? 1. Add a sulphonylurea? 3. Add pioglitazone? 4. Add insulin? 5. Add a GLP-1 receptor agonist? 6. Review in 6 months? Mr C 6 months later Age (years): 54 BMI (kg/m ): 30 25 Type 2 diabetes 2.5 years diagnosed: HbA 1c 63 52 mmol/mol (7%) Diabetes medication: Metformin 1000 mg BD; Canagliflozin 300mg OD; Dulaglutide 1.75 mg Once Weekly eGFR(ml/min): 80 Lipids (mmol/L): TC 4.8 HDL LDL 3.0 TG 2.2 1.0 Blood pressure (mmHg): 125/80 Lifestyle: Smokes 10/day; 20 units alcohol/week; eats out regularly QW: Once weekly dose Resources • Phcuk.org – resources – Sugar Infographics • Management of Type 2 Diabetes 2018. A Consensus Report by ADA and EASD • Trend-uk.org – patient information leaflets • Diabetes.org.uk – professionals – Information Prescriptions • Lowcarbprogram.com – 40 day Kickstart Programme • Carbs and Cals World Foods • GP Notebookeducation.com