The Role of Metformin in the Treatment of Insulin Resistance …二甲双胍治疗胰岛素抵抗的作用…

Hypoglycemia: benefits and risks (DCCT)
Severe hypoglycemia (per 100 patient-years)
100 Intensive group
80
60
40 Conventional group
20
0
5
6
7
8
9
10
HbA1c (%)
Retinopathy (per 100 patient-years)
Severe Hypoglycemia in T2DM is as Common as in T1DM with Increasing Duration of Insulin Therapy
Proportion reporting at least one hypoglycaemic episode
(France, Germany, UK, USA)
Direct impact of reduced productivity
Indirect impact through increased treatment cost
Productivity loss: up to $90 per event Following a daytime event:
9
9
9
6
3
0.4
0.7
0
Standard
Intensive
p<0.001
6
3.0
3
1.0
0 Standard Intensive
p<0.001
6 4.0
3
0
Standard
Intensive
p<0.01
Intensive glucose lowering contributes to an increased risk of hypoglycemia by 2- to 3-fold, particularly in advanced type 2 diabetes
HbA1c (%)
Retinopathy risk
Hypoglycaemia rate
Adapted from DCCT Research Group N Engl J Med 1993;329:977–86
Hypoglycemia in the Management of Diabetes
1. The impact of hypoglycemia:
1.0
0.8
0.6
0.4
0.2
0.0
SU <2 yr >5 yr &lUK Hypoglycaemia Study Group. Diabetologia 2019;50:1140–7
Socioeconomic Consequences of Non-Severe Symptomatic Hypoglycemia in Type 2 Diabetes
Hypoglycemia in Diabetes: the limiting factor to optimal control
June 7, 2019
Kenneth Cusi, MD, FACP, FACE Professor of Medicine
Chief, Division of Endocrinology, Diabetes & Metabolism University of Florida, Gainesville
1. ADVANCE. N Engl J Med 2019;358:2560–72; 2. ACCORD. N Engl J Med 2019;358:2545–59; 3. VADT. N Engl J Med 2009;360:129–39
ADVANCE: Severe Hypoglycemia is Associated with Increased Risk of Adverse Outcomes
Definition of Hypoglycemia
• Low plasma glucose causing neuroglycopenia • Clinical definition of hypoglycaemia:
– Mild: self-treated – Severe: requiring help for recovery
with insulin or an insulin secretagogue (CDA)3
ADA, American Diabetes Association; CDA, Canadian Diabetes Association; EMA, European Medicines Agency 1. EMA. CPMP/EWP/1080/00. 2019; 2. ADA. Diabetes Care 2019;28:1245–9; 3. Yale et al. Canadian J Diabetes 26:22–35
Cardiovascular disease (it either)22c(o9.n5)tributes to520a(d4.8v)erse outcomes or is a mar3k.7e9r(2.36–6.08)
Data given are number and percentage of annual national estimates of hospitalisations. Data from the NEISS-CADES project.
ER visits n=265,802/Total cases n=12,666
Budnitz et al. N Engl J Med 2019;365:21
Hypoglycemia Accounts for Most Endocrine-related Emergency Hospital Admissions
Budnitz et al. N Engl J Med 2019;365:21
Retinopathy
11
12
13
16 14 12 10 8 6 4 2 0 14
DCCT, Diabetes Control and Complications Trial DCCT Research Group. N Engl J Med 1993;329:977–86
The Physician’s Dilemma
• 18% lose an average of 10 h of work time
• 24% miss a meeting/deadline
Following a nocturnal hypoglycaemic event:
• 23% arrive late/miss work • 32% miss a meeting/deadline • 15 h of work are lost
Rate of severe hypoglycaemia (per 100 patient-years)
Rate of progression of retinopathy (per 100 patient-years)
100 12
80 10
60
8
40
6
4
20 2
0
0
5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5
Major microvascular events
24 (11.5)
1107 (10.1)
2.19 (1.40–3.45)
“Severe hypoglycemia (SH) was strongly associated with
Death from any cause increase4d5 (1r9is.5k) of a ran9g86e(9o.0f) adverse clinical outcomes3.…27 (2.29–4.65)
• Out-of-pocket costs due to extra/special groceries, extra testing supplies and transport: ~$25 per month
Brod et al. Value Health 2019;14:665–71
Hypoglycemia in the Management of Diabetes
1. The impact of hypoglycemia:
– Its is common and adds cost to diabetes treatment – Increases morbidity and mortality
Intensive Insulin Therapy is Associated with Increased Incidence of Severe Hypoglycemia
• Biochemical definition of a low plasma glucose:
– 3.0 mmol/L (<54.1 mg/dL) (EMA)1 – 3.9 mmol/L (≤70 mg/dL) (ADA)2 – 4.0 mmol/L (<72 mg/dL) for clinical use in patients treated
Zoungas at al. N Engl J Med 2019;363:1410–8, for the ADVANCE Collaborative Group
ADVANCE: Severe Hypoglycemia is Associated with Increased Risk of Adverse Outcomes
Severe hypoglycemia