diabetes

2. How to achieving
essential Glycemic
Control in Diabetics of
low Socio-economic
areas?
Dr. Speaker
Consultant Medical Specialist
In charge Diabetes Clinic
XXXHospital
Rawalpindi

6. Pakistan
• The highest comparative diabetes prevalence rates in 2021 are
reported in Pakistan (30.8%)
• Within the last two years, 13.6 million more people have become
diabetics in the country, which is extremely alarming
• Over 26.9% of individuals residing in Pakistan who are suffering from
diabetes are undiagnosed
• As per the IDF statistics, diabetes is responsible for 400,000 deaths in
Pakistan in the year 2021

7. Glycemic Control- What Does 1% Mean In Clinical Practice

8. Decision Cycle for patient-centred Glycaemic Management in type 2
Diabetes

14. Choosing A Gliptin
Why Choose
A Gliptin?
DPP4
Inhibition:
What
Matters?
Efficacy of
DPP4
inhibitors
Use of Gliptins in
comorbid
conditions
a. Renal Impairment
b. Hepatic Impairment
c. CV Disease
Future
Perspective

15. Why Choose A Gliptin?
• Addresses major core defects of diabetes
• Only class of OADs to directly reduce beta
cell stress
• Improve insulin production and reduce
glucagon secretion
• Excellent synergy with Metformin
• Doesn’t cause hypoglycemia or weight
gain
• Efficacy at par with other conventional
OADs when compared from similar
baselines
• Overall safety better than SUs
Efficacy
Control

16. Why combine gliptin with metformin

17. Sitagliptin and Metformin: 5 Years Durability Data
• Gliptin-Metformin
combination with a 5
years durability data
• Superior to SU+Met
Sitagliptin added to Metformin was more effective than SU added to Met (HbA1c difference of 1.4%), was more durable in keeping blood
sugar under control over 5 years (while SU started losing control after 1.5 years), and was safer, being associated with less hypoglycemia
and unlike SU-Met, was not associated with increase in BMI
N=624
Adapted from Derosa G, D'Angelo A, Maffioli Pet al. Pharmacol Res. 2015 Oct;100:127-34Sitagliptin in type 2 diabetes mellitus: Efficacy after five years of therapy.

18. Sitagliptin + Metformin Provide Superior Glycemic Control
18
10%
(mean 10.4%)
9% and <10%
(mean 9.4%)
8% and <9%
(mean 8.4%)
<8%
(mean 7.6%)
HbA1C
Change
from
baseline
at
Week
54
(%)
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
Sitagliptin 100 mg (28/43/19/16)
Metformin 500 mg bid (32/39/30/16)
Metformin 1000 mg bid (40/53/33/8)
Sitagliptin 50 mg + metformin 500 mg bid (39/49/38/21)
Sitagliptin 50 mg + metformin 1000 mg bid (33/60/43/17)
*Mean change  SE: APT Population.
Williams-Herman D et al. Poster presented at 2007 ADA Annual Meeting; Chicago, IL.
Sitagliptin + Metformin provides substantial and durable glycemic control
with a 3% reduction of HBA1c
Initial Combination Therapy with Sitagliptin and Metformin: Change From Baseline in A1C at Week 54 by Baseline A1C Subgroups*

19. Lower risk of Hypoglycemia
Sitagliptin was associated with a lower risk of hypoglycemia
Diabetes Obes Metab. 2011

20. 20.1%
5.5%
0.0
5.0
10.0
15.0
20.0
25.0
Glimepiride Sitagliptin-Metformin
Patients
with
>1
Hypoglycemic
Episodes
%
73%
© 2016 The Authors. Journal of Diabetes published by John Wiley & Sons Australia, Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.
73% Safer in Risk of Hypoglycemia

21. Weight Loss in comparison to Sulfonylureas
Diabetes Obes Metab. 2011
Sitagliptin was associated with a weight loss.

22. Gliptins in comorbid conditions

23. The cardiovascular safety of incretin-based therapies: a
review of the evidence
Cardiovascular Diabetology volume 12, Article number: 130 (2013)

24. Sitagliptin + Metformin has well established
Cardiovascular Safety
1. Cardiovasc Diabetol. 2013;
2. UKPDS 34. Lancet 2008
3. N Engl J Med 2015;

25. CV Safety of Sitagliptin:
• Only OAD with CV Safety Outcome
study not suggesting increased risk
(significant or numerical) of any CV
event (nonfatal MI, nonfatal Stroke,
h-HF)
• Pooled safety analysis/Meta-analysis
also indicative of an overall cardio-
safe profile
Efficacy
Control

26. Sitagliptin + Metformin exerts beneficial
effect on Lipid profile
Sitagliptin + Metformin exerts beneficial effect on glycemic and lipid profile,
provides pleiotropic effect in inhibiting cardiovascular events.
Pak J Med Sci. 2019 Mar-Apr;
Drug Saf. 1999 Jun;20(6)

27. Gliptin in Renal Impairment
Indication
All Gliptins (except Gemi)
are currently indicated in
all stages of CKD
Dosage
Some gliptins (Sita, Vilda,
Saxa) are effective at a
lower dose while some
gliptins (Lina, Teneli,
Gemi) continue to be
given at the same dose
in renal impairment to
achieve similar drug
concentration
Safety
Most of the gliptins are generally
“considered safe” in CKD. However the
same needs to be further backed by
evidence for some gliptins
Unique Benefits
Multiple small studies suggest a
promising positive effect of gliptins on
the renal health. Larger studies
warranted.

29. Gliptins in Hepatic Impairment
Approved Indications
Gliptin Use in Hepatic Impairment
Sitagliptin Indicated in patients with hepatic impairment
(Mild/Moderate Hepatic Impairment, Lack of data in Severe Hepatic Impairment)
Vildagliptin
Should not be used in Hepatic Impairment
(Concerns of raised Hepatic enzymes)
Saxagliptin Indicated in patients with hepatic impairment
Linagliptin Indicated in patients with hepatic impairment
Teneligliptin
Hepatic dysfunction included in the “Clinically significant adverse
reactions”
References adapted from Individual Prescribing Information

30. Co-morbid conditions: Cardiovascular Disease
DPP4i: Cardiovascular Data (Clinical)
Type What was analyzed What was seen
Mechanistic/
Small studies
Focused on the effect of gliptins on
cholesterol, IMT, cardiac risk markers, Blood
pressure, hemodynamics (LV Function etc.)
Mostly promising results suggesting
CV benefits with some of the
Gliptins
Pooled Analysis/
Meta-analysis
Analysis of the RCTs of various gliptins (Non-
CV efficacy and Safety studies) to see if there
was any effect on the CV outcomes
Mostly positive results, especially
when compared with the SUs
Cardiovascular
Outcome Studies
Whether adding the molecule increases the
risk of CV event, especially if the benefits of
glucose lowering is nullified
Mostly neutral results (no increase
in major adverse cardiovascular
events)

31. DPP4i and risk of Heart Failure: 5 years follow up
• Of the DPP4i 83 % were on sitagliptin, 15 % on saxagliptin, and 3 % on linagliptin
• n=79,538 (18 % with baseline CVD)
Hazard Ratio (95 % CI)
(Non-DPP4i as a referent group)
CVD 0.88 (0.77–1.01)
MI 0.84 (0.56–1.25)
Coronary Revascularization 0.93 (0.76–1.14)
Stroke 0.85 (0.60–1.20)
Heart Failure 0.84 (0.70–1.01)
CVD w/o Heart Failure 0.91 (0.77–1.08)
All Cause Death 0.90 (0.55–1.46)
Cohort study that included initiators of DPP4i and non-DPP4i treatments
Adapted from Kim SC, Glynn RJ, Liu J, Everett BM, Goldfine AB. Acta Diabetol. 2014 Dec;51(6):1015-23. Dipeptidyl peptidase-4 inhibitors do not increase the risk of
cardiovascular events in type 2 diabetes: a cohort study.

32. Evidence and Experience
Publications in PubMed
indexed Journals
1. Sitagliptin 2004
2. Vildagliptin 924
3. Saxagliptin 607
4. Linagliptin 386
5. Teneligliptin 99
Approval in major markets
1. Sitagliptin: All Major Markets
2. Vildagliptin: Not Approved in
USA
3. Saxagliptin: All major markets
4. Linagliptin: All major markets
5. Teneligliptin: Not in EU or USA
1. Indexed in www.pubmed.com, accessed on 13/06/2018
2. Registered in ClinicalTrials.gov, accessed on 13/06/2018
Registered Clinical Trials2
1. Sitagliptin 439
2. Vildagliptin 237
3. Saxagliptin 129
4. Linagliptin 152
5. Teneligliptin 23
Documentation Global Availability Experience in Humans

33. Sitagliptin a logical option for essential
control
 Sitagliptin has the ability to:
 Maintain beta cell mass,
 Effectively controls blood glucose levels,
 Improves cardio-renal function
 Reduces CV risk factors e.g. Lipid Profile
 Has low incidence of hypoglycemia.
 In addition, combination therapy implementing less than maximal doses of metformin permitting a
minimum of metformin-associated gastrointestinal effects.
 The fixed-dose combination allows physicians to modify the regimens of patients with inadequately
controlled glucose levels with metformin monotherapy without increasing pill burden.
Daniala L. Weir et al; Sitagliptin Use in Patients With Diabetes and Heart Failure: A Population-Based Retrospective Cohort Study; Journal of American
College of Cardiology, Volume 2, Issue 6, December 2014, Pages 573 – 582.