15th MGSD Congress
27-29 April, 2017
The fundamentals when managning
type 2 diabetes
J. Vassallo (Malta)
Organized by
15th MGSD Congress
27-29 April, 2017
Question
Do you consider tight glycemic control a
priority in management of type 2 diabetes?”
YES
NO
It depends on the patients
Organized by
The fundamentals when
managing type 2 diabetes
Josanne Vassallo MD PhD FRCP
Division of Diabetes and Endocrinology
University of Malta Medical School
Mater Dei Hospital, Malta
o
T2DM is a Progressive Disease
Advances in therapeutic options
in DM in the last100 yrs
Animal
insulin
(1923)
1920
1930
Metformin
(1959)
1940
1950
1960
SU
(1955)
Human
insulin
(1980)
1970
1980
Repaglinide
/Nateglinide
(1998/2001)
1990
Gliptins
/DPP-IV
Inhibitors
(2003)
2000
Acarbose
(1990)
2010
Liraglutide
(2009)
Analogue insulins
(1996+)
Rosi/Pioglitazone
(1999/2000)
BID, twice daily; OW, once weekly
Exenatide
BID
(2007)
Exenatide
OW
(2011)
SGLT2
Inibitors
(2012)
2020
Lixisenatide
(2013)
Standard Management of T2DM
Treatment Intensification
Insulin
Oral + Insulin
Oral Combination
Diet, Exercise, Oral Monotherapy
Adapted from Riddle MC. Endocrinol Metab Clin North Am 2005; 34: 77-98.
+
+
+
American Diabetes Association Standards of Medical Care in Diabetes.
Approaches to glycemic treatment. Diabetes Care 2017; 40 (Suppl. 1): S64-S74
 Is optimizing glycaemic
control important in T2 DM?
Targets
The lower the better?
 Target A1c
 BP control
 Lipid levels
Windows of opportunity?
Earlier is essential
Effects of more vs less intensive glycemic control
Ray KK et al. Lancet. 2009;373:1765-72
Is there an evidence base for
tight and timely control of blood
glucose?
UK Prospective Diabetes Study
20-year Interventional Trial from 1977 to 1997
 5,102 patients with newly-diagnosed type 2 diabetes
recruited between 1977 and 1991
 Median follow-up 10.0 years, range 6 to 20 years
 Results presented at the 1998 EASD Barcelona meeting
10-year Post-Trial Monitoring from 1997 to 2007
 Annual follow-up of the survivor cohort
 Clinic-based for first five years
 Questionnaire-based for last five years
Median overall follow-up 17.0 years, range 16 to 30 years
Legacy Effect of Earlier Glucose Control
After median 8.5 years post-trial follow-up
Aggregate Endpoint
1997
2007
12%
0.029
9%
0.040
Any diabetes related endpoint
RRR:
P:
Microvascular disease
RRR:
25%
P: 0.0099
Myocardial infarction
RRR:
P:
16%
0.052
15%
0.014
All-cause mortality
RRR:
P:
6%
0.44
13%
0.007
RRR = Relative Risk Reduction, P = Log Rank
24%
0.001
Conclusions
• Despite an early loss of glycemic differences, a
continued reduction in microvascular risk and
emergent risk reductions for myocardial infarction and
death from any cause were observed during 10 years
of post-trial follow-up
• A continued benefit after metformin therapy was
evident among overweight patients.
Importance of commencing intensive glucose control early
Subgroup analyses by baseline characteristics for the outcome of ESRD
RR -46%
RR -84%
RR -66%
Wong MG et al. Diabetes Care. 2016;39(5):694-700
Hypoglycaemia – an unwanted
side effect of tight control
Major hypoglycaemia, weight gain and
intensive glucose lowering in major trials
TRIAL
Major Hypoglycaemia
Annual Rate (%)†
Weight gain at end of Follow up
(Kg)‡
Intensive
Standard
Intensive
Standard
0.6*
0.3*
0.1
-0.8
ACCORD
3.2
1.0
3.5
0.4
VADT
4.2
1.8
8.1
4.1
ADVANCE
Major hypoglycaemia was uncommon in ADVANCE and only reported in
231 patients among 11,140 followed for 5 years, 150 in intensive group
and 81 in standard control group
* Represents 0.7 and 0.4 events per 100 patient
years for intensive versus standard treatment
† Data from Turnbull et al Diabetologia 2009, August 6
HbA1c targets should be individualized
Goal of therapy
 In general: HbA1c <7%
 In the individual patient: HbA1c as close to 6% as possible without significant
hypoglycemia
Call to action: HbA1c 7%
Less stringent goals may be appropriate for:
 Patients with a history of severe hypoglycemia
 Patients with limited life expectancies
 Very young children or older adults
 Individuals with co-morbid conditions
Nathan DM, et al. Diabetes Care 2009;32 193-203.
Other cardiovascular risk factors
 Blood pressure
 Lipid levels
Steno 2: study design
• Study design: randomized, open, parallel trial in Denmark
• Microvascular study: effect of intensive multifactorial strategy on the development of nephropathy
• Macrovascular study: effect of intensive mutifactorial strategy on the incidence of CV events
• Treatments: conventional multifactorial treatment versus intensified multifactorial treatment
• Patients: 160 patients with T2D and microalbuminuria
• Follow-up: 7.8 years
Conventional group assigned to GPs
N=80
n=160
Microvascular
Macrovascular
Endpoint examinations
4 years
8 years
N=80
Intensive group assigned to Steno Diabetes Center
Gaede et al. Lancet. 1999 Feb 20;353(9153):617-22.
Steno 2: Characteristics
Gliclazide
Gæde P, et al. Multifactorial Intervention and Cardiovascular Disease in Patients with Type 2 Diabetes. N Engl J Med 2003;
348:383-93.
Control of risk factors (LS, BP, Lipids and Glucose) in
type 2 diabetes patients
Gaede P, et al. Multifactorial intervention and cardiovascular disease in pts with type 2 diabetes N Engl J Med
2008;358:580–91.
STENO 2: 21 years follow-up
Median survival time in original intensive-therapy group
was 7.9 years longer than in the conventional-therapy
group
Median difference in survival before first CVD event
was 8.1 years in favor of the original intensive-therapy
group
Gaede P et al. Diabetologia. 2016;59(11):2298-307.
STENO 2: 21 years follow-up
In Conclusion…….
Treatment Strategies for Patients
with Diabetes
Optimum glycemic control
 Dietary and lifestyle changes
 Exercise
 Medication
Prevention of microvascular complications
 Control of glycemia
 Control of blood pressure
 Monitoring and screening
Prevention of CHD, MI, and other macrovascular complications
 Control dyslipidemia:  LDL-C,  HDL-C,  TG
 Dietary and lifestyle changes and exercise
 Drug therapy with statins
Adapted from Powers AC. In Harrison’s Principles of Internal Medicine. 15th ed. New York: McGraw-Hill,
2001:2109-2137; American Diabetes Association Diabetes Care 2002;25(suppl 1):S74-S77.
Implications of Optimal Management
– for the System
Multidisciplinary F/U
Intensive monitoring
Regular health checks
Regular screening
Regular Intervention
Increasing medication costs
Escalating healthcare costs
Decreasing morbidity
and mortality
Improving quality of
life
Counteracting the
negative impact on
healthcare budgets of
DM complications.
Primary vs secondary
prevention
MODY in the
Maltese Islands
Thank you