Case 1:Poorly controlled type 2 diabetes on triple oral therapies Case 2:Morning hypoglycemia on premixed InsulinCase 3 Case 3:Newly diagnosed D.M Type1D.M or type 2 D.M ?

1. Case Studies In The
Management of Type 2
Diabetes
Nasser Al-Juhani, MD,FRCP (U.K),ArBIM.SBIM,PHMD
Consultant of Endocrinology & Metabolic diseases

2. Rreceived honoraria/consultation fees from AstraZeneca, Sanofi,
Eli Lilly, Novo Nordisk, Boehringer Ingelheim, Merck, AstraZeneca
and Pfizer.
DISCLOSURE

3. Case 1
Poorly controlled type 2 diabetes on
triple oral therapies

4. • A 55-year-old man with
type 2 diabetes for 10 years.
• Background retinopathy
• C/O poluria,polydepsia and 4 Kg
weight loss over past 3 months
• Wt=70,Ht=166 cm, BMI is 25.4.
• Metformin 1 g BID po
• Empagliflozin 10 mg OD po
• Sitagliptin 100 mg od
• Normal renal & liver function
• eGFR 58
• Urine:albuminuria + ,no ketones
• ECG: normal
• HbA1c is 9.0 %.
1.1 What is your next treatment (s)
recommendation?
A. Add Gliclazide MR
B. Add repaglinide
C. Add pioglitazone
D. Add basal insulin
E. Add GLP-1 RA
Case 1

5. When to consider insulin in T2DM?
• Uncontrolled on 3 agents start INSULIN
• When 2 OAD being used-maximally
& AIC is not at goal ≥ 7%
If AIC < 8.5
Add 3rd OHA or insulin
or GLP-1RA
If AIC >8.5
Add insulin (or
GLP-1RA)
3rd OHA :
 AIC drop 1%
 Greater cost

6. • A 55-year-old man with
type 2 diabetes for 10 years.
• Background retinopathy
• C/O poluria,polydepsia and 4 Kg
weight loss over past 3 months
• Wt=70,Ht=166 cm, BMI is 25.4.
• Metformin 1 g BID po
• Empagliflozin 10 mg OD po
• Sitagliptin 100 mg od
• Normal renal & liver function
• eGFR 58
• Urine:albuminuria + ,no ketones
• ECG: normal
• HbA1c is 9.0 %.
1.2 What will you select as the basal
insulin for this patient?
A. NPH
B. Glargine U100
C. Glargine U 300
D. Detemir
E. Premixed insulin 70/30
Case 1

7. The Next Generation of Basal Insulin
with a Smoother PK/PD Profile than Lantus®
TOUJEO
•Smoother PK/PD
profile than Lantus®
•Full 24h coverage
•Less hypos than
Lantus
•Improved patient
experience
LANTUS
• Once daily
• Less hypos
than NPH
• Treat to target
NPH
PK/PD Profile: Pharmacokinetic/Pharmacodynamic Profile

8. Starting Basal Insulin+ OHA(S)
• Glargine 300 (Toujeo®) : 14 u at bedtime ,10 pm (0.2 U X 70 kg)
• Continue oral agent (s) at same dosage
• Daily FBG
• REQUEST PATIENT to increase basal dose 2 units
every 3 days to keep FBG target 80-130 mg/dl
 During 6 & 12 months of follow-up
• Glaring -U300 dose was titrated to 45-U daily
• FBG averages 106 -115 mg/dL
• A1C = 6.6 – 6.9 %
5-18

9. At 2-year follow-up
• His weight increased 2 kg, BMI is 26.
• Background retinopathy/nephropathy
• Normal renal & liver function
• Has irregular eating habits; occasionally
misses meals during the day
• HbAic 8.1%
Case ……Con”d
57 yr man,DM2,Failure of 3 OADs Plus Basal insulin
Fasting
2H Post
breakfast
Pre
Lunch
2H Post
Lunch
Pre
dinner
2H Post
dinner
HbA1c
110 175 120 220 140 170 8.1%
• Metformin 1 g BID
• Empagliflozin 10 mg OD
• Sitagliptin 100 mg OD
• Glargine-U300) 45-U od pm
Target1 <110 <180 <130 <180 <130 <180 <7
Suspect PPH, IF FBG<130 mg/dl & AIC> goal >7%

10. A. Increase the dose of basal insulin
B. Add bolus insulin with lunch meal
C. Add bolus insulin with 3 main meals
D. Switch to twice daily premixed insulin
E. Add GLP-1 Receptor agonist
Choose the most suitable option?

11. How much rapid-acting analog at meal will you initiate?
Glulisine (Apidra®)
4 Units
OR
0.1-U/kg

12.  Start Glulisine (Apidra®) 4 -U at lunch
 INSTRUCT PATIENT to adjust rapid-acting analog dose
at meal by 2 units every 3 days until BG in the target.
 Keep 2HPBG target 140-180 mg/dl
 FBG target 80-130 mg/dl
 Target HbAIC <7%
How do you adjust a rapid-acting analog at meals??

13. CASE 1 ……Con”d
6-Month Follow-Up
• Glargine 300 (Toujeo®) 46-U 10 pm
• Glulisine (Apidra®) 16-U at lunch and, patient is doing well
• Continue metformin 1 gm bid po/ Empagliflozin 10 mg od
• may D/C or continue Sitagliptin (more cost)
• A1C = 6.8%
• Patient feels well, has infrequent “ minor hypoglycemia,”
• Over time, if postprandial glucose becomes elevated at meals
other than lunch, add pre-meal insulin at that meal

14. Holman RR et al. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med 2007; 357(17): 1716–1730
>6 out of 10 basal insulin patients
will need another insulin to reach
target
After 1 year of treatment with basal oral therapy,
How many patients out of 10 will need another insulin?

15. When to target post-prandial blood glucose?
 ADJUST BASAL insulin Controls pre-meal glucose
 1st Fix the Fasting & Pre-dinner (PRE-MEALS)
 80-130 mg/dl (4.4-7 mmol/l)
 ADJUST BOLUS insulin :
 if HbAic<8.0 %, the contribution of post-meal glucose becomes more
 Pre-meal may be at target, but postmeal glucose values are high
 Monitor 2-HPP
 2hr PPG< 140-180 mg/dl (<10 mmol/l)
** AVOID HYPOGLYCEMIA <4 mmol/l( < 70mg/dl)
Controls post-meal glucose

16. Patient Not at Target with Basal
Insulin
Move on to
Multiple Daily Injections
Or
twice daily PreMix
Or
GLP-1 RA

17. Case 2
Morning hypoglycemia
on premixed Insulin

18.  55-year-old man
 T2DM x 10 years
 Painful sensory neuropathy & nephropathy
 eGFR 55, Creatinine 0.9 mg/dl
 Erratic work schedule
 sweating at some nights
 Metformin XR 1500 mg od
 Dapagliflozin 10 mg od
 Premixed insulin analogue:
- 70/30 50 U am and 40 U pm
 Hbaic 7.5%
 FBG 200-280 mg/dl
• Morning hyperglycemia :
– Check blood sugar at bedtime and
between 2-3 a.m.
– Or Continuous glucose monitoring
Case 2

19. 19
BF PRE
LUNCH
PRE
DINNER
HS 0300
MON 260 112 155 140 56
TUE 225 110 168 126 47
WED 280 88 153 120 60
THU 190 106 136 130 59
Case 2

20. Classification of severity:
Non-severe versus severe symptomatic:
• Non-severe: Patient has symptoms but can
self-treat and cognitive function is mildly
impaired
• Severe: Patient has impaired cognitive
function sufficient to require external help
to recover (Level 3)
Reclassification of hypoglycaemia1–3
1. Seaquist ER et al. Diabetes Care 2013;36:1384‒1395.
2. International Hypoglycaemia Study Group. Diabetes Care 2017;40:155‒157.
3. Frier BM. Nat Rev Endocrinol 2014;10:711‒722.
Alert value for
hypoglycemia
Plasma glucose
3.9 mmol/L (< 70
mg/dl) and no
symptoms
Serious clinically
important
biochemical
hypoglycemia
Plasma glucose
3.1 mmol/l
(55 mg/dl)
Level 1 Level 2

21. Cause Bedtime 2-3 a.m. Fasting
Insufficient dinner rapid
acting dose/carbohydrate
consumption at night
High High High
Somogyi effect Normal Low High
Dawn phenomenon Normal Normal High
Morning hyperglycemia

22. Case 2
Shifting from premixed to Basal-Bolus insulin
For recurrent nocturnal HYPOGLYCEMIA
 TDD= 90 U/day
 80% of 90 U is 72 U
 50% as basal: Glargine 300 (Toujeo®) – 36 units od 10:00 pm
 36 U divided for three meals, (largest dose may given at largest meal) :
 12 U before breakfast
 12 U before lunch
 12 U before dinner

23. Case 3
Newly diagnosed D.M
Type1D.M or type 2 D.M ?

24.  20-year-old male with newly
diagnosed DM
 6 kg weight loss & polyuria for 1
month
 Brother had T2DM
 BMI 34.4 , acanthosis nigricans
 Lab results:
 BG 340 mg/Dl (18.8
mmol/l); A1C, 13%
 Creatinine, 0.8 mg/dL
 Ketones -ve
 Anion gap, normal
In addition to Lifestyle modification
What is your next treatment
recommendation?
A. Metformin
B. Metformin plus Gliclizide
C. Metformin plus empagliflozin
D. Metformin plus liraglutide
E. insulin
Case 3

25. When should insulin be started in T2DM?
Newly diagnosed T2DM:
• ADA/EASD 2020
Consider
initial injectable combination
GLP-1 RA+Basal insulin
or
prandial/basal insulin
IF HbAIC 10% or 2% above target

26. Case 3
20 Yr old male Newly diagnosed D.M,BMI 34.4,
AIC=13% (cont.)
Type 1 D.M or type 2 D.M ?

27. Physical exam
• Obese / acanthosis nigricans
suggest DM2
• Thin suggest DM1
Family history
• More with DM 2 but occurs
also with DM 1
Complication
• Suggests undiagnosed DM 2
Age at onset
• <30 year
• >30 year
Differentiating Type 1 Vs. Type 2 DM

28. • Fasting serum C-peptide levels
• Normal or High C-peptide :
• DM1 (with honey moon) or DM2
Follow up :SMBG
• If insulin dose is reduced and no
ketones, may consider a trial of
stopping insulin
• If glucose high or ketones+ , resume
insulin
Low C-peptide :
DM1 or late DM2- Insulin
 Testing for antibodies
 - GAD-65
 - Islet-cell
 - IA2
 - Insulin
-ZS
• High…DM1
• Normal…Idiopathic DM1 or DM2
Differentiating Type 1 Vs. Type 2 DM

29. Conclusions
Insulin Treatment in Type 2 Diabetes
• Basal treatment NPH or (glargine100 or 300) , detemir, degludec
Start 10 U and titrate
• Bolus treatment premeal (Lispro/glulisine/aspart)
Start at 4 U premeal and titrate;
• Premixed therapy
• Start at 10 U BID and titrate
• Basal bolus therapy
• Start at 0.5 U/kg, 40-50% basal, 20% bolus each meal