This document summarizes recent updates on the treatment of type 2 diabetes mellitus. It discusses the pathophysiology of type 2 diabetes and reviews commonly used drug classes like sulfonylureas, thiazolidinediones, metformin, and insulin. It then introduces newer drug classes like SGLT2 inhibitors and GLP-1 receptor agonists. It also discusses the use of bariatric surgery and new basal insulins like insulin glargine U300 and insulin degludec. Finally, it considers whether GLP-1 receptor agonists should replace metformin as the first-line oral therapy for type 2 diabetes given their superior efficacy but higher cost compared to generic metformin.

1. Updates On the Treatment of
Type 2 Diabetes Mellitus
By
Omar Mahmoud Mohamed Kamal
Supervised by:
Prof. Dr. Alaa Wafa
2017

2. Elective Module
Six weeks
Under supervision of Prof. Dr. Alaa Wafa
At the diabetes and endocrinology department, specialized
medical hospital ,Mansoura University .

3. Pathophysiology of T2DM
Mainly peripheral insulin resistance
and inadequate insulin secretion.
Obesity
Insulin
Resistance
More insulin
secretion to
overcome
resistance
More
obesity
More
resistance
Debilitation
of pancreas
beta cells
inadequate
insulin
secretion.
Increased
glucagon
production

4. Quick review of well known drugs
and lines of ttt for T2DM.

5. Sulphonylurea:
• Promotes insulin
secretion.
Thiazolidinedios
(glitazones) :
• Insulin sensitizer
Alpha-glucosidase
inhibitors :
• Impair carbohydrate
digestion
• Slow glucose
absorption
Metformin:
• Up till now it is
considered the first
line drug for
treatment of T2DM.
• ↓ hepatic glucose
production .
• Main side effect is
anorexia .
Insulin
• Ultra short insulin
• Short acting "soluble“
• intermediate acting
insulin
• Long acting insulin
analogues
• Biphasic (mixture)
Life style therapy
• Diet
• Exercise
• Sleep
• Smoking cessation
• 25% of T2DM
patients can kept off
of medication with
diet and exercise
only

6. OLD treatment algorithm for T2DM
Monotherapy
Dual therapy
Triple therapy

7. Recently introduced drugs

8. Sodium glucose co-transporter-2 inhibitors:
Are the most recent addition to the oral therapeutic
agents.

9. Mechanism of action
• So it reduce hyperglycaemia in patients with T2DM.
• The increase in glucosuria and diuresis results in a reduction in weight
and blood pressure.
• It is an independent mechanism of insulin, there is low risk for
hypoglycaemia, and no risk of debilitation of the beta cells.
Adverse Effects
• Four-to fivefold increased risk of genital & urinary tract infections.
• SGLT2i-induced ketoacidosis esp. in T1DM (due to Insulin dose reduction
and stress)

10. Incretin-Based Therapies:
• GLP1 secreted by small intestine, increase insulin secretion
and inhibit glucagon in response to nutrient inputs .
• However, endogenous human GLP-1 has a short half-life (2–
3 min) due to breakdown in the circulation by dipeptidyl
peptidase (DPP)-4.
• So pharmaceutical development took two routes: inhibition
of the DPP-4–degrading enzyme and creation of DPP-4–
resistant GLP-1 receptor agonists (GLP-1 RAs).

11. GLP-1 RAs:

12. Adverse Effects
• The main adverse effect is nausea.
• All RA-GLP-1 should not be used in patients with history of pancreatitis.
• Injection site reactions.
• ↓ HbA1c, fasting plasma glucose.
• protect against myocardial ischemia .
• protecting renal function by increasing diuresis .

13. DPP-4 Inhibitors
Adverse Effects
• Should not be used in patients with history of pancreatitis.
• Joint pain.

14. Bariatric surgery

15. Bariatric surgery
 Candidates :patients with a morbid obesity or those with a BMI > 35
kg/m2.
 Clinical studies demonstrate improvement in insulin resistance and β-cell
function and high rates of type 2 diabetes remission after gastric bypass .
 These observations support the recommendations for bariatric surgical
management of appropriately selected severely obese patients with type 2
diabetes.

16. New basal insulin
As β-cell function decreases with time , oral anti-diabetic drugs no longer
provide sufficient glycemic control
Basal insulin are one of the recommended steps in type 2 diabetes treatment
intensification.

17. Insulin glargine U300
• Approved by (FDA) in 2016.
• Insulin glargine U300 is a newer strength dosage of
Lantus U100.
• The pharmacokinetic and pharmacodynamic profiles
of the U300 are more stable and prolonged.
• The risk for nocturnal hypoglycemia is lower.
• It has no peak and produces a relatively stable level
lasting more than 24 hours.

18. Insulin degludec
• It has a duration of action of up to beyond 42 hours.
• Compared with other long-acting insulins , degludec profile is
flatter (has no peak ) with a half life greater than 25 h, and
action that exceeds 42 h, which results in a reduction of
nocturnal hypoglycaemia.
• It offers much greater flexibility over when doses can be taken
at different times of day without affecting glycemic control .

19. Should GLP-1 RAs Replace
Metformin as first-line therapy
in Type 2 Diabetes treatment
Algorithm??
Yes!!

20. • But Metformin is generic and inexpensive, but GLP-1 RAs are still under
patent and, therefore, expensive.

21. DIABETES MANAGEMENT
ALGORITHM –2017

24. Thank You