Diabetes update presentation Kotwal and Desouza

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Diabetes Update 2020Case Studies in Diabetes

Anupam Kotwal, MBBSAssistant Professor

Cyrus Desouza, MBBSProfessor and Chief

Division of Diabetes, Endocrinology and MetabolismUniversity of Nebraska Medical Center

Learning objectives1.Modify diabetes therapies based on

diabetes complications and comorbidities

2.Adjust insulin regimen based on glycemic control

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DisclosuresAnupam Kotwal: Nothing to disclose

Cyrus Desouza:• Novo Nordisk• AstraZeneca• Bayer

Case 1A 57-year-old man with type 2 diabetes for 12 years, hypertension, dyslipidemia, CAD and MI status post stent placement 9 months ago. He takes metformin, statin, aspirin, lisinopril. His BMI is 38 kg/m2 and HbA1c is 8.4%. What is the next best step in diabetes management?

1. Add DPP-4 inhibitor2. Add GLP-1 receptor agonist3. Add SGLT-2 inhibitor4. Add Insulin glargine5. Add Sulfonylurea

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Case 1A 57-year-old man with type 2 diabetes for 12 years, hypertension, dyslipidemia, CAD and MI status post stent placement 9 months ago. He takes metformin, statin, aspirin, lisinopril. His BMI is 38 kg/m2 and HbA1c is 8.4%. What is the next best step in diabetes management?

1. Add DPP-4 inhibitor2. Add GLP-1 receptor agonist3. Add SGLT-2 inhibitor4. Add Insulin glargine5. Add Sulfonylurea

Pharmacologic Approaches to Glycemic Management: Standards of Medical Care in Diabetes - 2020. Diabetes Care 2020;43(Suppl. 1):S98-S110

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LEADER (Liraglutide)

Marso, S. P., et al. (2016). "Liraglutideand Cardiovascular Outcomes in Type 2 Diabetes." New England Journal of Medicine 375(4): 311-322.

Primary outcome: First occurrence of cardiovascular death, nonfatal MI, or nonfatal stroke

SUSTAIN-6 (Semaglutide)Marso, S. P., et al. (2016). "Semaglutideand Cardiovascular Outcomes in Patients with Type 2 Diabetes." New England Journal of Medicine 375(19): 1834-1844.


Gerstein, H. C., et al. (2019). "Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial." The Lancet 394(10193): 121-130.

REWIND (Dulaglutide)

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GLP-1 receptor agonist with proven CVD benefit• Liraglutide > Dulaglutide >

Semaglutide > Exenatide LAR

OR (2nd line)SGLT-2 inhibitor with proven CVD benefit• Empagliflozin > Canagliflozin

Case 2A 60-year-old man with type 2 diabetes for 8 years, hypertension, dyslipidemia, coronary artery disease, systolic heart failure (LVEF 35%), recently admitted with heart failure exacerbation. He takes metformin for diabetes. His BMI is 40 kg/m2 and HbA1c is 8.5%. What is the next best step in diabetes management?

1. Add DPP-4 inhibitor2. Add GLP-1 receptor agonist3. Add SGLT-2 inhibitor4. Add Insulin glargine5. Add Sulfonylurea6. Add Thiazolidinedione

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Case 2A 60-year-old man with type 2 diabetes for 8 years, hypertension, dyslipidemia, coronary artery disease, systolic heart failure (LVEF 35%), recently admitted with heart failure exacerbation. He takes metformin for diabetes. His BMI is 40 kg/m2 and HbA1c is 8.5%. What is the next best step in diabetes management?



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DAPA-HF (Dapagliflozin)

McMurray, J. J. V., et al. (2019). "Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction." New England Journal of Medicine 381(21): 1995-2008.

58% did NOT have DMPrimary outcome: Worsening HF (hospitalization or an urgent visit resulting in intravenous therapy for HF) or cardiovascular death

EMPA-REG (Empagliflozin)

Zinman, B., et al. (2015). "Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes." New England Journal of Medicine 373(22): 2117-2128.


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EMPEROR-Reduced(Empagliflozin)

Packer, M., et al. (2020). "Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure." New England Journal of Medicine.

Primary outcome: First occurrence of cardiovascular death or hospitalization for HF

Hospitalization for heart failure reduction• Dapagliflozin > Empagliflozin >

Canagliflozin• Dapagliflozin and Empagliflozin

improve worsening HF and CV death in patients without diabetes as well

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Case 3A 62 year-old woman with type 2 diabetes for 7 years, hypertension, diabetic nephropathy, CKD. She takes metformin 1000 mg daily. Her BMI is 34 kg/m2, HbA1c is 8.2%, eGFR is 42 ml/min/1.73m2, urine albumin/creatinine is 320 mg/g. What is the next best step in diabetes management?


Case 3A 62 year-old woman with type 2 diabetes for 7 years, hypertension, diabetic nephropathy, CKD. She takes metformin 1000 mg daily. Her BMI is 34 kg/m2, HbA1c is 8.2%, eGFR is 42 ml/min/1.73m2, urine albumin/creatinine is 320 mg/g. What is the next best step in diabetes management?


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CREDENCE (Canagliflozin)

Perkovic, V., et al. (2019). "Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy." New England Journal of Medicine 380(24): 2295-2306.

Primary outcome: ESKD (dialysis, transplantation, or sustained eGFR of <15 ml/min/1.73 m2), doubling of the serum Cr, or death from renal or cardiovascular causes

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DAPA-CKD (Dapagliflozin)

• Participants with eGFR 25-75 ml/min/1.73m2 and UACR 200-5000 mg/g (n=4304)

• Primary endpoint (eGFR decline >50%, ESKD, kidney or CVD death) significantly reduced by 39%

• HR 0.61 (95% CI 0.51–0.72; p=0.000000028)• All secondary endpoints met, including all-cause

mortality significantly reduced by 31%• Benefit was consistent in patients with and without

type 2 diabetes

“A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (Dapa-CKD).” ClinicalTrials.gov

LEADER (Liraglutide)

Time to first renal event (secondary outcome):Macroalbuminuria, doubling of serum Cr, ESRD, renal death

Marso, S. P., et al. (2016). "Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes." New England Journal of Medicine 375(4): 311-322.

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For patients with type 2 diabetes and CKD, with or without cardiovascular disease• Consider the use of an SGLT2 inhibitor shown

to reduce CKD progression (Canagliflozin is the only one with FDA indication) or, if contraindicated or not preferred, a GLP-1 receptor agonist shown to reduce CKD progression

Case 4A 75 year-old woman with type 2 diabetes for 20 years, hypertension, CKD (eGFR 50 ml/min/1.73m2), osteoporosis, dependent pedal edema. She has history of several UTI, and has poor appetite. She takes metformin. Her BMI is 24 kg/m2 and HbA1c is 8.1%. She refuses insulin. What is the next best step in diabetes management?

1. Add DPP-4 inhibitor2. Add GLP-1 receptor agonist3. Add SGLT-2 inhibitor4. Add Sulfonylurea5. Add Thiazolidinedione

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Case 4A 75 year-old woman with type 2 diabetes for 20 years, hypertension, CKD (eGFR 50 ml/min/1.73m2), osteoporosis, dependent pedal edema. She has history of several UTI, and has poor appetite. She takes metformin. Her BMI is 24 kg/m2 and HbA1c is 8.1%. She refuses insulin. What is the next best step in diabetes management?

1. Add DPP-4 inhibitor2. Add GLP-1 receptor agonist3. Add SGLT-2 inhibitor4. Add Sulfonylurea5. Add Thiazolidinedione


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If eGFR <45 ml/min/1.73m2

• Linagliptin• Dose-reduced Sitagliptin

Case 5A 55-year-old man with uncontrolled type 2 diabetes despite metformin and glargine once daily titrated to 40 units. HbA1c is 8.5%, AM fasting blood glucose range 120-140 mg/dL, prandial blood glucose range 180-200 mg/dL. His BMI is 36.8 kg/m2. What is the next best step in diabetes management?

1. Add meal-time rapid acting insulin2. Add DPP-4 inhibitor3. Add SGLT-2 inhibitor4. Add GLP-1 receptor agonist

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Case 5A 55-year-old man with uncontrolled type 2 diabetes despite metformin and glargine once daily titrated to 40 units. HbA1c is 8.5%, AM fasting blood glucose range 120-140 mg/dL, prandial blood glucose range 180-200 mg/dL. His BMI is 36.8 kg/m2. What is the next best step in diabetes management?

1. Add meal-time rapid acting insulin2. Add DPP-4 inhibitor3. Add SGLT-2 inhibitor4. Add GLP-1 receptor agonist

Supporting data

• ADA guidelines recommend to addition on non-insulin injectable before adding insulin in type 2 diabetes if no contraindications

• If patient is already on metformin and basal insulin, then addition of GLP-1 receptor agonist is associated with

• Similar HbA1c reduction• Less hypoglycemia• Weight loss v/s weight gain

1. Eng C, Kramer CK, Zinman B, Retnakaran R. Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis. Lancet. 2014

2. Billings LK, Doshi A, Gouet D, Oviedo A, Rodbard HW, Tentolouris N, Grøn R, Halladin N, Jodar E. Efficacy and Safety of IDegLira Versus Basal-Bolus Insulin Therapy in Patients With Type 2 Diabetes Uncontrolled on Metformin and Basal Insulin: The DUAL VII Randomized Clinical Trial. Diabetes Care. 2018

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Case 6A 65-year-old-woman with type 2 diabetes for 15 years, CKD (eGFR 28), CAD injects 20 units glargine at bedtime and 7 units aspart with meals. Pre-meal blood glucose target is 100-140 mg/dL. Her BMI is 24 kg/m2, HbA1c is 8%. Her blood glucose log for last 7 days is as below. What is the best next adjustment to her insulin regimen?

1. Increase glargine2. Increase breakfast aspart3. Increase lunch aspart4. Decrease dinner aspart5. No changes

Pre-breakfast

Pre-lunch

Pre-dinner

Bedtime

98 130 160 140

115 110 168 125

112 132 140 135

106 108 180 138

102 128 178 138

Case 6A 65-year-old-woman with type 2 diabetes for 15 years, CKD (eGFR 28), CAD injects 20 units glargine at bedtime and 7 units aspart with meals. Pre-meal blood glucose target is 100-140 mg/dL. Her BMI is 24 kg/m2, HbA1c is 8%. Her blood glucose log for last 7 days is as below. What is the best next adjustment to her insulin regimen?

1. Increase glargine2. Increase breakfast aspart3. Increase lunch aspart4. Decrease dinner aspart5. No changes

Pre-breakfast

Pre-lunch

Pre-dinner

Bedtime

98 130 160 140

115 110 168 125

112 132 140 135

106 108 180 138

114 128 178 138

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Principles of insulin dose adjustmentPrandial/meal-time insulin• BG should be in target

before the next meal

Long-acting/basal insulin• BG should stay level or

within 40 mg/dL overnight if not eating

Blood Glucose (BG) Before Breakfast:

Basal dose adjustment

40 mg/dL BELOW bedtime BG the night before

Decrease dose by 10%

Within 40 mg/dL of bedtime BG the night before

Continue current dose

ABOVE bedtime BG the night before (no snack)

Increase dose by 10%

Blood Glucose (BG) before NEXT meal

Prandial dose adjustment

Below goal range Decrease dose by 10%

Within goal range Continue current dose

Above goal range Increase dose by 10%

• “3-4 day pattern”• Seek the cause of hypoglycemia and adjust

insulin regimen accordingly

Take home pointsGLP-1 receptor agonists and SGLT-2 inhibitors with

beneficial effects on cardiovascular disease, heart failure and/or renal dysfunction should be preferred

Hypoglycemia risk and glycemic target should guide diabetes therapy

GLP-1 receptor agonist + basal insulin show similar HbA1c reduction with less hypoglycemia and more weight loss as compared to basal + prandial insulin

Insulin dose adjustment is based on recognizing a pattern of abnormal blood glucose

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Thank you

[email protected]: @kotwal_anupam

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Documents

Diabetes update presentation Kotwal and Desouza