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ANTI-HYPERGLYCEMIC DIABETES AGENTS: Outcomes Comparison Summary Table Glucose Lowering Agents J Bareham BSP, L Regier BSP BA, L Lu BSP © www.RxFiles.ca Sep 2015
Drug Class Sulfonylureas TZDs Meglitinides Incretin Related Agents Insulin in T2DM SGLT2 inh
Generic 
BRAND
Metformin
(MF)
GLUCOPHAGE,
GLYCON
Gliclazide
DIAMICRON
Glyburide
DIABETA
Pioglitazone
ACTOS
Rosiglita-
zone
AVANDIA
Acarbose
GLUCOBAY
Repaglinide
GLUCONORM
Nateglinide
STARLIX
Linagliptin
TRAJENTA
PO
Sitagliptin
JANUVIA
PO
Saxagliptin
ONGLYZA
PO
Liraglutide
VICTOZA
SC
Exenatide
BYETTA
SC
Range of
Intensity:
Less
(NPH at HS +
metformin)
Range of
Intensity:
More
(Multiple
daily doses)
Dapaglifozin
FORXIGA / FARXIGA
Canagliflozin
INVOKANA
Major trials to
support
findings/
Outcomes*
UKPDS-
33,34,80
(ADOPT;
some use in
ADVANCE)
ADVANCE UKPDS-
33,80
(ADOPT)
ProACTIVE
Ferwana M.
Meta-analysis
2013.
Meta-
analysis.
RECORD
interim,
ADOPT,
DREAM.
(Prevention
trial: Stop-
NIDDM)
-
SAVOR-TIMI 53: Saxagliptin vs placebo for CV outcomes, 2013.
(At 2yrs, n= >16,000: no benefit, some harms [HF admis otherwise CV neutral])
See RxFiles Trial Summary online at www.RxFiles.ca:
http://www.rxfiles.ca/rxfiles/uploads/documents/SAVOR-TIMI-53-Saxagliptin-CV-Outcomes-Trial-Summary.pdf
TECOS: Sitagliptin CV results neutral non-inferior to placebo, 2015
EXAMINE: Alogliptin vs placebo for CV outcomes, 2013;
(At median of 1.5yrs: neutral CV outcomes; no benefit, minimal harm)
UKPDS-33,80; ADVANCE,
ACCORD, VADT. (T1DM:
DCCT/EDIC)
(Also Boussageon et al. Meta-analysis.
BMJ 2011;343:d4169)
Empa-Reg: Empa.
↓ death & CV death.
CV outcome safety
trials in progress:
(CANVAS;
DECLARE-TIMI 58)
 Risk of
Death /
Major CV

in Obese
UKPDS-34
 Mortality
NNT=14/10yr
 long-term
 X??  ? ?
?
 3yr
TECOS
?
 2yr
SAVOR-TIMI 53
? ?
HR
?
?
XX?
?
(X: transient 
CV/stroke in 1st
mo with Cana-)
Effect on
A1C**     
 

       
Weight
(wt loss vs
neutral vs wt
gain)
 X X XX XX    ?     XX 
 Risk of
Hypoglycemia

X
? If less risk with
MR formulation
X X
Severe
occurs at
1.4%/yr
 
 

? ? ? ? ? 
XX
Rate of
1.8%/yr

Risk only when
given with
sulfonylurea or
insulin
?
X
 admissions
(observational)
X
 admissions
SAVOR-TIMI 53
? ? Risk of HF
/ Edema

(1st line in
stable HF)
  XX XX  
Emerging questions/concerns about ? HF risk
  ?
Effect on LDL     X          X
LDL: Cana > Dapa
Effect on GI
tolerability
X
Start low
& titrate


Rate of
1.8%/yr
  XX    

Nausea,
vomiting,
diarrhea

Nausea,
vomiting,
diarrhea
 

Nausea/ diarrhea
with dapaglifozin
Cost    X XX   X X X XX XX  XX XX
PPG

PPG,
Possible
benefit of
laxative
effect in
some?

PPG,
flexibility
with
meals
Other
May have
to hold or 
dose in
acute
illness/HF/
renal dysfx.
1
st
line for
obese
T2DM.
ADVANCE: used in
combination with
metformin.
Caution:
renal
function
(& older
adults).
X
 risk of fractures &
macular edema
Rosi: Restricted access- in
CDN (EDS) ( CV risk
concerns/controversy)
Pio: Risk of bladder ca
(NNH ~ 21,000/4yrs);
 avoid co-admin
with dapaglifozin.
TID dosing TID dosing
 PPG
X new agents – data on safety &
hard outcomes is still limited
Possible ↑ risk of infection e.g. URTI.
Risk of pancreatitis.
Linagliptin: Dose adjustment for renal
function not required.
 PPG
X new agents – outcome
& safety data still limited
Injection site irritation,
Risk of pancreatitis,
Possible risk of thyroid
cancer with liraglutide.
{new once weekly agents coming;
may have less GI adverse events.}

Fear/
perception of
insulin
injections
Fear/
perception
of insulin
injections
X: New agents
Outcome data
limited/concerns.
glucose in urine &
risk of UTI/yeast
infections /.
 intravascular
volume; BP.
?Bladder/prostate/
breast cancer.
Caution:renal fx,
ketoacidosis.
Overall    ? X?   ? ? ? ?



X
X?
*Drugs that lower blood glucose come with various levels of evidence regarding their balance of benefits & harms. This chart relies on current evidence, especially that from randomized
controlled trials that have evaluated patient oriented outcomes. Direct comparisons between agents have not been done so one is left to evaluate each drug for its relative advantages &
disadvantages.
**A1C will vary depending on dose, combinations & initial A1C. See also RxFiles Diabetes Landmark Trials Summary at: http://www.rxfiles.ca/rxfiles/uploads/documents/CHT-Diabetes-Landmark-Trials-Links.pdf
Individualize approach to
balance potential benefits &
harms. Over aggressive
pursuit of targets can 
mortality ACCORD
Canagliflozin ,
Dapagliflozin, &
Empagliflozin
JARDIANCE
: all
avail : CDN & USA.
An Advantage
 
Neutral
 X
A Disadvantage
XX 35
[Glipizide GLUCOTROL
USA
SPREAD-DIMCAD]
[Glipizide  risk vs MF,
NNT=10/5yr] SPREAD-DIMCAD

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Diabetes agents-outcomes-comparison-summary-table

  • 1. ANTI-HYPERGLYCEMIC DIABETES AGENTS: Outcomes Comparison Summary Table Glucose Lowering Agents J Bareham BSP, L Regier BSP BA, L Lu BSP © www.RxFiles.ca Sep 2015 Drug Class Sulfonylureas TZDs Meglitinides Incretin Related Agents Insulin in T2DM SGLT2 inh Generic  BRAND Metformin (MF) GLUCOPHAGE, GLYCON Gliclazide DIAMICRON Glyburide DIABETA Pioglitazone ACTOS Rosiglita- zone AVANDIA Acarbose GLUCOBAY Repaglinide GLUCONORM Nateglinide STARLIX Linagliptin TRAJENTA PO Sitagliptin JANUVIA PO Saxagliptin ONGLYZA PO Liraglutide VICTOZA SC Exenatide BYETTA SC Range of Intensity: Less (NPH at HS + metformin) Range of Intensity: More (Multiple daily doses) Dapaglifozin FORXIGA / FARXIGA Canagliflozin INVOKANA Major trials to support findings/ Outcomes* UKPDS- 33,34,80 (ADOPT; some use in ADVANCE) ADVANCE UKPDS- 33,80 (ADOPT) ProACTIVE Ferwana M. Meta-analysis 2013. Meta- analysis. RECORD interim, ADOPT, DREAM. (Prevention trial: Stop- NIDDM) - SAVOR-TIMI 53: Saxagliptin vs placebo for CV outcomes, 2013. (At 2yrs, n= >16,000: no benefit, some harms [HF admis otherwise CV neutral]) See RxFiles Trial Summary online at www.RxFiles.ca: http://www.rxfiles.ca/rxfiles/uploads/documents/SAVOR-TIMI-53-Saxagliptin-CV-Outcomes-Trial-Summary.pdf TECOS: Sitagliptin CV results neutral non-inferior to placebo, 2015 EXAMINE: Alogliptin vs placebo for CV outcomes, 2013; (At median of 1.5yrs: neutral CV outcomes; no benefit, minimal harm) UKPDS-33,80; ADVANCE, ACCORD, VADT. (T1DM: DCCT/EDIC) (Also Boussageon et al. Meta-analysis. BMJ 2011;343:d4169) Empa-Reg: Empa. ↓ death & CV death. CV outcome safety trials in progress: (CANVAS; DECLARE-TIMI 58)  Risk of Death / Major CV  in Obese UKPDS-34  Mortality NNT=14/10yr  long-term  X??  ? ? ?  3yr TECOS ?  2yr SAVOR-TIMI 53 ? ? HR ? ? XX? ? (X: transient  CV/stroke in 1st mo with Cana-) Effect on A1C**                 Weight (wt loss vs neutral vs wt gain)  X X XX XX    ?     XX   Risk of Hypoglycemia  X ? If less risk with MR formulation X X Severe occurs at 1.4%/yr      ? ? ? ? ?  XX Rate of 1.8%/yr  Risk only when given with sulfonylurea or insulin ? X  admissions (observational) X  admissions SAVOR-TIMI 53 ? ? Risk of HF / Edema  (1st line in stable HF)   XX XX   Emerging questions/concerns about ? HF risk   ? Effect on LDL     X          X LDL: Cana > Dapa Effect on GI tolerability X Start low & titrate   Rate of 1.8%/yr   XX      Nausea, vomiting, diarrhea  Nausea, vomiting, diarrhea    Nausea/ diarrhea with dapaglifozin Cost    X XX   X X X XX XX  XX XX PPG  PPG, Possible benefit of laxative effect in some?  PPG, flexibility with meals Other May have to hold or  dose in acute illness/HF/ renal dysfx. 1 st line for obese T2DM. ADVANCE: used in combination with metformin. Caution: renal function (& older adults). X  risk of fractures & macular edema Rosi: Restricted access- in CDN (EDS) ( CV risk concerns/controversy) Pio: Risk of bladder ca (NNH ~ 21,000/4yrs);  avoid co-admin with dapaglifozin. TID dosing TID dosing  PPG X new agents – data on safety & hard outcomes is still limited Possible ↑ risk of infection e.g. URTI. Risk of pancreatitis. Linagliptin: Dose adjustment for renal function not required.  PPG X new agents – outcome & safety data still limited Injection site irritation, Risk of pancreatitis, Possible risk of thyroid cancer with liraglutide. {new once weekly agents coming; may have less GI adverse events.}  Fear/ perception of insulin injections Fear/ perception of insulin injections X: New agents Outcome data limited/concerns. glucose in urine & risk of UTI/yeast infections /.  intravascular volume; BP. ?Bladder/prostate/ breast cancer. Caution:renal fx, ketoacidosis. Overall    ? X?   ? ? ? ?    X X? *Drugs that lower blood glucose come with various levels of evidence regarding their balance of benefits & harms. This chart relies on current evidence, especially that from randomized controlled trials that have evaluated patient oriented outcomes. Direct comparisons between agents have not been done so one is left to evaluate each drug for its relative advantages & disadvantages. **A1C will vary depending on dose, combinations & initial A1C. See also RxFiles Diabetes Landmark Trials Summary at: http://www.rxfiles.ca/rxfiles/uploads/documents/CHT-Diabetes-Landmark-Trials-Links.pdf Individualize approach to balance potential benefits & harms. Over aggressive pursuit of targets can  mortality ACCORD Canagliflozin , Dapagliflozin, & Empagliflozin JARDIANCE : all avail : CDN & USA. An Advantage   Neutral  X A Disadvantage XX 35 [Glipizide GLUCOTROL USA SPREAD-DIMCAD] [Glipizide  risk vs MF, NNT=10/5yr] SPREAD-DIMCAD