CV
HYPOGLYCAEMIA
WEIGHT
2019 update to the 2018 ADA/EASD consensus report recommends CVD
be considered early in treatment6
First-line therapy is metformin and comprehensive lifestyle changes (including weight management and physical activity)
Indicators of high-risk or established ASCVD, CKD or HF*
Consider independently of baseline HbA1c or individualised HbA1c target
ASCVD PREDOMINATES
HF OR CKD PREDOMINATES
- Established ASCVD
- Indicators of high ASCVD risk (age ≥55 years + LVH or
coronary, carotid, lower extremity artery stenosis >50%)
- Particularly HFrEF (LVEF <45%)
- CKD: Specifically eGFR 30-60 mL/min/1.73 m2
or UACR >30 mg/g, particularly UACR >300 mg/g
PREFERABLY
PREFERABLY
GLP-1 RA with proven CVD benefit†
SGLT2i with evidence of reducing HF and/or CKD
progression in CVOTs if eGFR adequate§
SGLT2i with proven CVD benefit†
if eGFR adequate‡
If SGLT2i not tolerated or contraindicated or if eGFR less
than adequate,‡ add GLP-1 RA with proven CVD benefit†
OR
OR
OR
OR
SGLT2i with proven CVD benefit†
if eGFR adequate‡
If SGLT2i not tolerated or contraindicated or if eGFR less
than adequate,‡ add GLP-1 RA with proven CVD benefit†
If HbA1c above target
If HbA1c above target
- If further intensification is required or patient is now
unable to tolerate GLP-1 RA and/or SGLT2i, choose agents
demonstrating CV safety:
- Avoid TZD in the setting of HF
- Choose agents demonstrating CV safety:
- For patients on a GLP-1 RA, consider adding SGLT2i with
proven CVD benefit† - DPP-4i if not on GLP-1 RA
- Basal insulinII
- TZD¶
- SU#
- For patients on a SGLT2i, consider adding GLP-1 RA with proven
CVD benefit† - DPP-4i (not saxagliptin) in the setting of HF (if not on GLP-1 RA)
- Basal insulinII
- SU#
*Actioned whenever these become new clinical considerations regardless of background glucose-lowering medications.
†Proven CVD benefit means it has label indication of reducing CVD events.
‡Be aware that SGLT2i labelling varies by region and individual agent with regard to indicated level of eGFR for initiation and continued use.
§Empagliflozin, canagliflozin, and dapagliflozin have shown reduction in HF and to reduce CKD progression in CVOTs. Canagliflozin has
primary renal outcome data from CREDENCE. Dapagliflozin has primary heart failure outcome data from DAPA-HF.
||Degludec or U100 glargine have demonstrated CVD safety.
¶Low dose may be better tolerated though less well studied for CVD effects.
#Choose later generation SU to lower risk of hypoglycaemia. Glimepiride has shown similar CV safety to DPP-4i.
CV
HYPOGLYCAEMIA
WEIGHT
In patients without indicators of high risk or established CVD,
consider hypoglycaemia6
2019 UPDATE TO THE 2018 ADA/EASD CONSENSUS REPORT:
If HbA1c above individualised target, proceed as below
COMPELLING NEED TO MINIMISE HYPOGLYCAEMIA
If HbA1c above target
DPP-4i
GLP-1 RA
SGLT2i*
TZD
SGLT2i*
SGLT2i*
GLP-1 RA
SGLT2i*
TZD
TZD
DPP-4i
DPP-4i
TZD
GLP-1 RA
OR
OR
OR
OR
OR
OR
OR
OR
OR
OR
OR
OR
TZD
TZD
DPP-4i
DPP-4i
TZD
GLP-1 RA
If HbA1c above target
If HbA1c above target
Continue with addition of other agents as outlined above
Consider the addition of SU† OR basal insulin:
ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes; CVD=cardiovascular disease; DPP-4i=dipeptidyl peptidase-4 inhibitor; GLP-1 RA=glucagon-like
peptide-1 receptor agonist; SGLT2i=sodium-glucose co-transporter 2 inhibitor; TZD=thiazolidinedione; eGFR=estimated glomerular filtration rate; CV=cardiovascular; SU=sulphonylurea.
- Choose later generation of SU with lower risk of hypoglycaemia
- Consider basal insulin with lower risk of hypoglycaemia‡
*Be aware that SGLT2i labelling varies by region and individual agent with regard to indicated level of eGFR for initiation and continued use.
†Choose later generation SU to lower risk of hypoglycaemia. Glimepiride has shown similar CV safety to DPP-4i.
‡Degludec/glargine U300 < glargine U100/detemir < NPH insulin.
CV
HYPOGLYCAEMIA
WEIGHT
In patients without indicators of high risk or established CVD, consider weight6
2019 UPDATE TO THE 2018 ADA/EASD CONSENSUS REPORT:
COMPELLING NEED TO MINIMISE WEIGHT GAIN OR PROMOTE WEIGHT LOSS
GLP-1 RA
SGLT2i†
SGLT2i†
GLP-1 RA
with good efficacy
for weight loss*
with good efficacy
for weight loss*
EITHER/
OR
If HbA1c above target
for weight loss*
If HbA1c above target
If quadruple therapy required, or SGLT2i and/or GLP-1 RA not tolerated or contraindicated,
use regimen with lowest risk of weight gain
PREFERABLY
DPP-4i (if not on GLP-1 RA) based on weight neutrality
If DPP-4i not tolerated or contraindicated or patient already on GLP-1 RA, cautious addition of:
- SU‡
- TZD§
- Basal insulin
ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes; CVD=cardiovascular disease; GLP-1 RA=glucagon-like peptide-1 receptor agonist;
SGLT2i=sodium-glucose co-transporter 2 inhibitor; eGFR=estimated glomerular filtration rate; SU=sulphonylurea; CV=cardiovascular; DPP-4i=dipeptidyl peptidase-4 inhibitor;
TZD=thiazolidinedione.
*Semaglutide > liraglutide > dulaglutide > exenatide > lixisenatide.
†Be aware that SGLT2i labelling varies by region and individual agent with regard to indicated level of eGFR for initiation and continued use.
‡Choose later generation SU to lower risk of hypoglycaemia. Glimepiride has shown similar CV safety to DPP-4i.
§Low dose may be better tolerated though less well studied for CVD effects.
