Tailoring type 2 diabetes management to each patient: case studies 15th MGSD Congress 27-29 April, 2017 Tailoring type 2 diabetes management to each patient: case studies S. Al Sifri (Kingdom of Saudi Arabia) Organized by

Case Studies Saud Alsifri, MD, FACE Alhada & Taif Armed Forces Hospitals

Voting Cards to be used

Noora Middle-aged female Story of 2 years, First seen in January 2015, Last clinic visit February 2017

Patient Profile 56 years old Weight: 88Kg BMI: 30.5 kg/m2 Primary school teacher Married with two children Diagnosed with Type 2 diabetes for 10 years. Known with Hypertension, Dyslipidemia.

Past Clinical history At diagnosis: Few years after diagnosis: Started on lifestyle changes for few years, which brought her HbA1c from 8.9% to 7.5% and helped her to lose some weight. Few years after diagnosis: Metformin 500mg tid was added to lifestyle changes, in order to bring her HbA1c from 8.6% to 7.8%. However, Metformin caused gastrointestinal side effects, so slow-release metformin (Metformin XR) was prescribed in order to address these side effects. After a period of control, Noora’s HbA1c began to rise and the dose of metformin XR was uptitrated to 3 tablets od 10 years after diagnosis Although the patient initially achieved control, her HbA1c has increased again to 8.7%. Reluctant to Use Injections.

Physical Examination Height: 170 cm Weight: 88 kg BMI: 30.5 kg/m2 BP : 138/85 mmHg Pulse: 72 Fundoscopy: Grade I Neck: Thyroid not palpable Heart: Normal Lungs: Normal Abdomen: no murmurs Arteries: Normal Neuro: decreased vibration & monofilament in feet

Labratory results 8.6 mmol/L 4.0-8.0 mmol/L 300 mmol/L 80-350 mmol/L Test Results Normal values Glucose 8.6 mmol/L 4.0-8.0 mmol/L Uric acid 300 mmol/L 80-350 mmol/L Creatinine 90 µmol/L eGFR 80 ml/min 44-106 µmol/L K 3.8 mmol/L 3.5-5.0 mmol/L Na 136 mmol 135-145 mmol/l HbA1c 8.7% 4.0 – 6.0 % Urinalysis Neg. proteinuria Neg Alb/creat 1.0 mg/mmol 0.0 - 2.8 mg/mmol CK 125 30-213 u/l TSH 4.2 0.35-5.50 mUI/l LDL 2.6 mmol/L <3.0 mmol/L Total chol 6.8 mmol/L <5.20 mmol/L TG 1.8 mmol/L <1.70 mmol/L HDL 0.8 mmol/L >0.99 mmol/L Labratory results

Glycemic targets What would be your HbA1c Goal for her ? Between 7.0 -7.5 %! < 7 %! > 8 %! I’m happy with this HbA1c!

T2D management considerations for individualised treatment: ADA/EASD Position Statement 2015 HbA1c Less than 6.5% HbA1c 7% HbA1c more than 8% More stringent Less stringent Hyperglycaemia management approach Hypoglycaemia and AE risks Low High Disease duration Newly diagnosed Long-standing Life expectancy Long Short Important comorbidities Absent Few/mild Severe Established vascular complications Absent Few/mild Severe Patient attitude and expectations Highly motivated Less motivated Resources and support system Readily available Limited T2D, type 2 diabetes; AE, adverse event; CV, cardiovascular; ADA, American Diabetes Association; EASD, European Association for the Study of Diabetes. Adapted from Inzucchi SE et al. Diabetes Care 2015;38:140−149

Clinical course before January 2015 9 Time (Years) 8 7 6 HbA1c (%) 8.9 7.5 Diet & lifestyle changes Diagnosis 2007 8.6 7.8 3 12 Metformin XR 3tabs od Metformin 500mg tid 8.7 CLINIC VISIT Jan 2015 Visit

Current clinical challenge Metformin XR alone, at the current dosage, is not providing Noora with the glycaemic control she requires . Despite good initial weight loss, she has been unable to maintain her weight despite making lifestyle changes

Concerns for choosing treatment What is your main concern at this time for Noora? Glycemic efficacy. The Hypoglycaemia Risk, and weight gain. CV Safety and Outcome. All of the above.

Treatment options What would be your preferred choice for Noora’s glycemic control? Continue Metformin, and Add DPP-4 I ! Continue Metformin, and Add Liraglutide! Continue Metformin and add Pioglitazone ! Continue Metformin, and Add SU!

EASD/ADA Guidelines. Diabetes Care 2015

Considerations Will the treatment choice... Provide the glycaemic control that Noora’s requires. Minimise the risk of hypoglycaemia and other S/E Helps Noora maintain her body weight

Clinical Course (cont.) Noora continued on Metformin XR 3 tablets od and started on Gliclazide MR 60 mg od. After 4 months her A1c dropped to 7.3 %, and Weight 89 Kg, BP 132/85 mmgh, Reports no Hypoglycemia.

Treatment options What would you do at this time ? Continue the same ! Change Gliclazide MR into another SU ! Increase the dose of Gliclazide MR ! Continue Gliclazide MR and add a new agent !

Clinical Course (cont.) Gliclazide MR increased to 90 mg od and continued Metformin. 4 months later, HbA1c 6.8 %, Weight 87 Kg, No hypos. Continued on Same treatment. 6 months later, seen in OPD, HbA1c 6.9 %, Weight 86 Kg, No hypos.

Outcome till February 2017 Gliclazide MR 90mg was added to metformin XR 3 tab. Noora has regained glycaemic control HbA1c decreased to 6.9% Weight maintained at 86 Kg BP 130/80 mmHg Noora has also benefited from the additional features of Gliclazide MR She has maintained her weight She has not experienced hypoglycaemia.

Clinical course: HbA1c HbA1c (%) Time (months) Diagnosis Jan 2015 8 7 6 HbA1c (%) 8.9 7.5 Diet & lifestyle changes Diagnosis 8.5 7.8 3yrs 10 yrs 6yrs 9yrs metforminXR 3tabs od Add Gliclazide MR 60mg od Metformin 500mg tid 9 Inc. Gliclazide MR 90mg od Continue Same 8.7 Continue same Continue Same 7.3 6.8 6.9 Jan 2015 Feb 2017 30 36 40

Ali Young middle-aged male Newly diagnosed, First seen in August 2016, Last clinic visit January 2017

Patient Profile 48 years old Weight: 80Kg BMI: 27.3 kg/m2 Government officer Married with three children Diagnosed with Type 2 diabetes for 2 months. Not following diet, and minimal daily activity. No known chronic illness.

Physical Examination Height: 178 cm Weight: 80 kg BMI: 27.3 kg/m2 BP : 125/75 mmHg Pulse: 78 Funduscopic: Normal Neck: Thyroid not palpable Heart: Normal Lungs: Normal Abdomen: no murmurs Arteries: Normal Neuro: Normal

Laboratory results 10.6 mmol/L 4.0-8.0 mmol/L 60 µmol/L eGFR 90 ml/min Test Results Normal values Glucose 10.6 mmol/L 4.0-8.0 mmol/L Creatinine 60 µmol/L eGFR 90 ml/min 44-106 µmol/L K 4.1 mmol/L 3.5-5.0 mmol/L Na 140 mmol 135-145 mmol/l HbA1c 9.0% 4.0 – 6.0 % Urinalysis +ve proteinuria Neg Alb/creat 4.0 mg/mmol 0.0 - 2.8 mg/mmol

Glycemic targets What would be your HbA1c Goal for him ? < 6.5 % ! Between 7.0 - 7.5 % ! > 7.5 %! I’m happy with this HbA1c!

Treatment options What would be your preferred choice for Ali’s glycemic control? Lifestyle modification only! LSM and DPP-4I! LSM and start Metformin! LSM, Metformin and SUs !

Clinical Course (cont.) Given Instructions on diet and exercise by D. educator, and started on Metformin IR 500 mg od, to be increased gradually over the coming 4 weeks to reach Metformin 1000 mg bd. Came back after 1 month reporting nausea, vomiting, bloating, and diarrhoea with metformin.

Clinical Course (cont.) Metformin IR was replaced with Metformin XR 750 mg od, to be gradually increased by 1 tab. Every week. Return back to his regular clinic visit after 3 months. Reporting nausea, stomach pain, and bloating with metformin XR, even with one tablet.

Clinical Course (cont.) At this time, HbA1c 8.8 %, weight: 80 Kg. Trying his best to maintain Lifestyle modification, but very hard for him. Taking no medications.

Treatment options What would be your preferred choice for Ali’s glycemic control at this time? Continue Lifestyle modification only! Start Gliclazide MR 60 mg od! Start DPP-4I ! Start SU and Basal Insulin!

Clinical Course (cont.) He was started on Gliclazide MR 60 mg od and stressed over diet, exercise and SMBG twice daily. Came after 4 months, HbA1c 7.1 %, weight 78 kgs, No hypos, maintaining diet and exercise. Renal function: e-GFR; 90 ml/min, UACR; 3.6 mg/mmol.

Treatment options What would you suggest for his glycemic control? Keep the same! Add DPP-4I ! Increase Gliclazide MR 90 mg od! Add Basal Insulin!

Clinical Course (cont.) His Gliclazide MR dose increased to 90 mg od along with maintaining LS changes. After 3 months, HbA1c 6.6 %, weight 78 kgs, No hypos, following diet and exercise. Renal function: e-GFR; 90 ml/min, UACR; 1.6 mg/mmol, Negative Proteinuria.

Summary

Pros and cons of 2nd line diabetes therapies1 Sulfonylurea Gliclazide MR Pioglitazone SGLT-2 I Insulin GLP-1 RA DPP-4 I Efficacy ++ ** +++ Cardiovascular outcome studies Yes Yes2 No (in progress) Hypoglycaemia as consequence of individual drug Higher* Low Weight gain NO Wt Loss Wt loss Disadvantages Hypoglycaemia Being in SU class Fluid retention Increased risk of osteoporosis and fractures3 Bladder cancer4 UTIs, Genital Infections, Dehydration Gastrointestinal side effects Long-term safety not established DPP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1. 1Adapted from Nathan DM, et al. Diabetologia. 2009; 52: 17–30; 2Ruige JB, et al. Circulation. 1998; 97: 996–1001; 3Lecka-Czernik B. Curr Osteoporos Rep. 2010; 8: 178–184 4EMA/CHMP/568262/2011 press release accessed July 23rd 2011.. *Compared to non-insulin secretagogues

Summary of Canadian Guidelines: Checklist 2016 CHOOSE initial therapy based on glycemia START with Metformin +/- others INDIVIDUALIZE your therapy choice based on characteristics of the patient and the agent REACH TARGET within 3-6 months of diagnosis 39

Thank You HOPE= SAUD Amie Vanderford