Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
John MF Adam
Cost,
Efficacy Hypoglycaemia Weight Side effects comorbidities,
(HbA1c)
pt. preference
1American Diabetes Association. Diabetes Care 2014;37(Suppl 1):S14–80; 2Inzucchi et al. Diabetes Care 2012;35:1364–79
The challenge of blood glucose control in diabetes
mellitus
Hypoglycaemia /
weight gain
HbA1c
control
HbA1c=haemoglobin A1c
Jacob et al. Diabetes Obes Metab 2007;9:386–93; Khunti & Davies. Diabetes Obes Metab 2010;12:474–84;
Wright et al. J Diabetes Complications 2006;20:395–401
The challenge of blood glucose control in diabetes
mellitus
Hypoglycaemia / HbA1c
weight gain control
HbA1c=haemoglobin A1c
Jacob et al. Diabetes Obes Metab 2007;9:386–93; Khunti & Davies. Diabetes Obes Metab 2010;12:474–84;
Wright et al. J Diabetes Complications 2006;20:395–401
Metformin SU TZD DPP - 4 SGLT2-
Innhibitors Innhibitors
Therapy for Diabetes Mellitus and Related Disorders, 6th ed. In: Umierrez GE (ed). American
Diabetes Association 2014
Pharmacokinetics and pharmacodynamics of DPP-4
inhibitors
Aschner P. Dipeptidyl-peptidase 4 inhibitors. In: Umierrez GE (ed). Therapy for Diabetes Mellitus
and Related Disorders, 6 th ed. American Diabetes Association 2014; 387-400
CARDIOVASCULAR EFFECT
Aloglitpin EXAMINE
Saxagliptin SAVOR
Sitagliptin TECOS
Vildagliptin ??????
If HbA1c target not achieved after ~3 months of monotherpay, proceed to 2-drug combintaion (order not meant to
denote any specific preference-choice dependent on a variety of patient- and disease-specififc factors):
If HbA1c target not achieved after ~3 months of dual therpay, proceed to 3-drug combintaion (order not meant
to denote any specific preference-choice dependent on a variety of patient- and disease-specififc factors):
A1c < 9% consider monotherpy; A1c > 9% consider dual therapy; A1c > 10% consider combination injectable therapy
ALGORITME PENATALAKSANAAN HIPERGLIKEMI
ADA 2018
3. Kadar A1C > 10% atau glukosa plasma sewaktu > 300 mg/dL,
sebaiknya KOMBINASI DENGAN INSULIN
INHIBITION OF DPP – 4
INCREASES ACTIVE GLP-1
Meal
Insulin action GLP-1 as an
Intestinal secretagog, is glucose
GLP-1
release dependent
Active
GLP-1
DPP-4
Study Purpose:
To assess the profile of vildagliptin and the fixed-dose combination of
vildagliptin/metformin relative to comparator oral anti-diabetic drugs (OADs)
in patients with type 2 diabetes in a real-world setting
Primary Objective:
To determine the proportion of patients on vildagliptin add-on dual therapy or
vildagliptin/metformin (fixed-dose) relative to comparator OAD dual therapy
responding (A1c drop >0.3%) to 12 months’ treatment without any of the
predefined tolerability issues:
➢peripheral edema, or
➢hypoglycemic events, or
➢discontinuation due to GI events, or
➢weight gain (>5%)
Mathieu C, et al. Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: A real-life
worldwide observational study (EDGE). Int J Clin Pract. 2013 Oct;67(10):947-56.
27 Countries participating in EDGE
Europe
Austria, Belgium, Czech Republic, Germany, Greece, Netherlands,
Portugal, Slovakia, Sweden, Bulgaria, Luxembourg, Russia
Middle East
Jordan, Palestine, Lebanon,
Bahrain, Kuwait, Oman
United Arab Emirates
12
Adapted from Mathieu C, et al. Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2
diabetes: A real-life worldwide observational study (EDGE). Int J Clin Pract. 2013 Oct;67(10):947-56.
Study design (EDGE study)
• Multinational, multicenter, post-authorization, prospective, observational, cohort study
• EDGE (Effectiveness of Diabetes control with vildaGliptin and vildagliptin/mEtformin)
involved nearly 46,000 patients (intention-to-treat [ITT] population) from nearly 3,000
centres in 27 countries from Europe, Central and Latin America, Asia and the Middle
East
Monotherapy failure
*Vildagliptin cohort: T2DM patients newly initiating vildagliptin as add-on dual therapy or newly initiating vildagliptin/metformin (fixed-dose) from non-
vildagliptin monotherapy
**Comparator OAD cohort: T2DM patients newly initiating therapy with oral anti-diabetic therapies other than vildagliptin (defined as SU, metformin, TZDs,
metiglinides, α-glucosidase inhibitors) as add-on dual therapy except as add-on to vildagliptin, other DPP-4 inhibitors, or GLP-1 mimetics/analogues
AE = adverse event; BL = baseline; OAD = oral anti-diabetic drug; T2DM = type 2 diabetes mellitus; TZDs = thiazolidinediones
Mathieu C, et al. Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: A
real-life worldwide observational study (EDGE). Int J Clin Pract. 2013 Oct;67(10):947-56.
The EDGE Study
One of the largest T2DM observational studies ever conducted in a real-world setting
12-month observational, multicenter, post-authorisation, prospective cohort study, which included
45,868 patients from 27 countries worldwide
BL=baseline
OAD comparators used: metformin, SU, TZD, AGI, glinide; other DPP-4 inhibitors and GLP-1 analogues are excluded
Adapted from Mathieu C, et al, Int J Clin Pract 2013;67:947-56
Vildagliptin as add-on metformin in real-life setting:
-1.1% HbA1c reduction
Broadly consistent with the decrease seen in randomized controlled trial settings
Consistent efficacy
SU = sulphonylurea
Al Arouj M., et al. Int J Clin Pract. 2013; doi 1111/ijcp 12243
VIRTUE: data from >1300 fasting T2DM patients pooled
from 10 countries
Al Arouj M., et al. Int J Clin Pract. 2013; doi 1111/ijcp 12243
VIRTUE: Numbers of patients from participating countries
Country Vildagliptin SU
n (%) n (%)
Bangladesh 50 (7.3) 49 (7.8)
Egypt 124 (18.1) 126 (20.0)
India 58 (8.5) 51 (8.1)
Pakistan 121 (17.7) 121 (19.2)
Indonesia 23 (3.4) 19 (3.0)
UAE 79 (11.5) 48 (7.6)
Lebanon 172 (25.1) 152 (24.1)
Kuwait 12 (1.8) 17 (2.7)
Oman 31 (4.5) 22 (3.5)
Saudi Arabia 14 (2.0) 26 (4.1)
All* 684 (100.0) 631 (100.0)
*18 patients excluded, as they were not treated with a medication of interest
SU = sulphonylurea
Al-Arouj M, et al. Abstract accepted for presentation at American Diabetes Association 73 rd Scientific
Sessions, June 21–25, 2013, Chicago, USA;
VIRTUE: prospective, multinational ‘real-world’ study design
Al Arouj M., et al. Int J Clin Pract. 2013; doi 1111/ijcp 12243
21
VIRTUE study: Fewer Hypoglycaemic Events with Vildagliptin
Compared To SUs
hypoglycaemic event
Patients (n) with ≥1
36
(5.4%)
4
0.5
Mean change in HbA1c
from baseline (%)
0.02
0
–0.24 –0.26
P<0.001‡
–0.5
†Thewithin and between treatment differences were based only on patients with HbA1c levels
assessed at both baseline and end of study. ‡Two-sample t test
SU = sulphonylurea; HbA1c = haemoglobin A1c
Al Arouj M., et al. Int J Clin Pract. 2013; doi 1111/ijcp 12243
23
VIRTUE: Changes in Body Weight
0
Mean body weight change
–0.13
from baseline (kg)
–0.5
–0.63
–0.76 P<0.001‡
–1
–1.5
†The mean change in body weight and the between treatment difference were based only on patients
with body weight assessments at both baseline and end of study. ‡Two-sample t test
SU = sulphonylurea
Al Arouj M., et al. Int J Clin Pract. 2013; doi 1111/ijcp 12243
24
VIRTUE: Conclusions
•A large study assessing the relative benefit of DPP4 inhibitor in
Muslim patients with T2DM fasting during Ramadan
Al Arouj M., et al. Int J Clin Pract. 2013; doi 1111/ijcp 12243
Conclusion