At the meeting the last ADA day Julio Rosenstock from Dallas prof of Medicine presented the empagliflozin results in T1 DM.
He said in the beginning that new insulin formulations and advanced delivery system with more precise CGM and sesnor-augmented insulin pumps (SAP) are just not enough to optimally manage T1DM. Glucose control for patients with T1DM is a tuff job. We need somethiong More in the therapy.
This session was the only session during this 2 hr workshop at the ADA meeting. Just to show that the ADA organisation committe made a priority. Around 8000 people were in the audience with many questions and enthuasism.
The basis for SGLT2 inhibition with its potential benefits are
1. Efficacy based on insulin-dependent glucose lowering effects
2. Reduced glucose variability related to changes in glucose filtration
3. Potential for low risk of hypoglycemia
4. Lower insulind oses mainly boluses
5. Weight loss. Less systolic blood pressure
6. Potential reno-protection by reducing intra-glomerular pressure
7. Potential cardio- and vesselprotection from Empa-study Sept 2015 with 38% less cardiovascular mortality
The study design of EASE-1 was randomized, double-blind, placebo-controlled, 4 week trial at 2 sites in Austria and Germany with empa (Jardiance) 2,5 mg, 10 mg and 25 mg with 20 patients in every arm and placebo
The results was 6.7 mmol/mol lower HbA1c at 4 week p 0.0005, for Jardiance 25 mg, 5,4 mmol per mol lower for 10 mg Jardiance and 5,3 lower HbA1c for Jardiance 2,5 mg per day p 0.0006
In the EASE-2 and Ease-3 trials there was 52 weeks study with 1 week screening, 6 weeks insulin optimiazation period and then 2 weeks run in period with CGM before the 52 week study. CGM was used in the last 2 weeks before week 26 and 2 weeks at the 52 week period. Jardiance 2,5, 10 and 25 mg pere day was used and comparison with placebo.
Main inclusion criteria was
Age 18 years or older
T!DM for 12 months or more and C-peptide less than 0.7 ng/ml
On MDI for at least 12 months or CSII least 5 months and insulin needs of 1,5 Units/kg or more
eGFR 30 or more ml/min/kvm 1,73
HbA1c 7,5 or more DCCT standard and less than 10% at randomization (HbA1c around 58-80 mmol per mol)
Baseleine characteristics 53% females, mean age 45 years, blood pressure 125/76, mean BMI 29, mean eGFR 95
Summary of key results, just summary, and no levels were presented
1. HbA1c reduction yes for 2,5, 10 and 25 mg Jardiance
2. Weight loss yes for all mg
3. No increase in symtomatic hypoglycemia yes for all mg
4. No increase in severe hypoglycemia for all mg
5. Confirmed DKA no increase in 2,5 mg Jardiance, small increase in 10 and 25 mg Jardiance per day
6. Less glucose variability from CGM
Could Jardiance 2,5 mg per day have unique lower dose provide the right efficacy/safety balance för SGLT2-I in T1DM? "Did we found the Sweed Spot"?
1. Adjunctive therapies to insulin are a REAL Unmet Need in T1DM
2. SGLT-I´s insulin-dependent mechanism does work in T1DM
3. People with T1DM on SGLT2-I can tell the Difference
4. Increased DKA with SGLT2-I is low but it is REAL and Serious
5. SGLT2-I in T1DM shuld only be used with a DKA Mitagion Plan
CV Benefits in T2DM at high CV Risk
38% less CV death
35% less heart hispitalizations for heart failure
39% less new or wrosening nephropathy
6. People with T1DM live longer but CVD is increaseed 2-4 fold
7. Pragmatic CVOTs with SGLT2-I in T1DM at high risk are needed!
Good advice from the audience
1. Do not skip the breakfast or lunch or dinner. Beacuse of then high very risk for DKA. It is all a question of glucose/insulin dosing. Try to be very very dangerous with alcohol in any forms because of higher risks for DKA
2. Use of pen insulin with technical problems with insulin pump or when higher blodd glucose or if blood ketones are coming up. Start early. Do not wait. Bring insulin pens to job and when travelling. Always!
3. Stop using Jardiance with gastroenteritis, fever, viros or other "sick-day" feelings. Start again when you are fit for ready again
It you do not feel well. Whatever the reason, fatigue etc, do check blood glucose. Take carbohydrate and insulin. Check 4 hrs again. Have blood keton test strips near you, also when working or tavelling, to prevent DKA
The professionals, and the patients, are looking forward to get the approval from FDA and European authorities EMEA for SGLT-2-I as an adjunctive therapy for motivated T1DM patients
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