Evidence of the Month

Tony OSullivan
Comment on:
ADA/EASD consensus statement and algorithm for the treatment of Type 2 diabetes

Nathan DM, Buse JB, Davidson MB, et al. Diabetes Care. 2009;32: 193-203. Nathan DM, Buse JB, Davidson MB, et al. Diabetologia. 2009;52:17-30.

Goals and methods

Statement updates joint ADA/EASD algorithm for initiating and adjusting therapy of Type 2 diabetes Based on clinical trial review and collective clinical judgement/experience Evaluates glucose-lowering capacity, extra-glycaemic effects that could reduce long-term diabetic complications, safety, tolerability, ease of use, and cost of each intervention

Provides treatment algorithm with tiers of well validated and less well validated interventions for Type 2 diabetes

Diabetes interventions by tiers

Tier 1 Interventions (well-validated core) Lifestyle changes to reduce weight/increase exercise (1.0-2.0)* Metformin (1.0-2.0) Insulin (1.5-3.5) Sulfonylureas (1.0-2.0) Tier 2 Interventions (less well-validated core) Thiazolidinediones (pioglitazone) (0.5-1.4) Glucagon-like peptide-1 (GLP-1) agonists (exenatide) (0.5-1.0) Others (less effective glucose reduction, less evidence, or costlier) -Glucosidase inhibitors (0.5-0.8) Glinides (0.5-1.5) Pramlintide (0.5-1.0) Dipeptidyl peptidase-4 (DPP-4) inhibitors (0.5-0.8)

*Numbers in parentheses are expected percentage point decrease in HbA1c with monotherapy

New ADA/EASD treatment algorithm for Type 2 diabetes

Tier 1: Well validated core therapies

At diagnosis:
Lifestyle + Metformin

Lifestyle + Metformin + Basal insulin

Lifestyle + Metformin + Intensive insulin

Lifestyle + Metformin + Sulfonylureaa STEP 2 STEP 3

STEP 1

Tier 2: Less well validated therapies

Lifestyle + Metformin + Pioglitazone No hypoglycaemia Oedema/CHF Bone loss Lifestyle + Metformin + GLP-1 agonistb No hypoglycaemia Weight loss Nausea/vomiting Lifestyle + Metformin + Pioglitazone + Sulfonylureaa

Lifestyle + Metformin + Basal insulin

Reinforce lifestyle interventions at every visit and check HbA1c every 3 months until HbA1c is <7 % and then at least every 6 months. The interventions should be changed if HbA1c is 7 %
aSulfonylureas bInsufficient

other than glibenclamide (glyburide) or chlorpropamide clinical use to be confident regarding safety

Comments on treatment choices

Tier 2 options may be considered when weight loss is major goal Exenatide is associated with weight loss Tier 2 options may be considered when hypoglycaemia is major concern

Pioglitazone and exenatide associated with less risk (rosiglitazone NOT recommended)
-Glucosidase inhibitors, glinides, pramlintide, and DPP-4 inhibitors appropriate for selected patients (not defined)

Drug combinations should be selected according to synergistic mechanisms and other interactions
Initiating or intensifying insulin generally preferred to addition of third oral agent

Clinical implications
Algorithm encourages flexibility and clinical judgement in Type 2 diabetes treatment Algorithm is cautious in use of newer treatments

Lack of head-to-head trials continues to impede informed comparisons of strategies

In severely uncontrolled diabetes, lifestyle + insulin is preferred regimen

Long-term ability to control diabetes or reduce cardiovascular complications still a concern