Sodium glucose cotransporter (SGLT) inhibitors are new oral antidiabetic medications shown to
effectively reduce glycated hemoglobin (A1C) and glycemic variability, blood pressure and body
weight without intrinsic properties to cause hypoglycemia in people with type 1 diabetes.
However, recent studies, particularly in individuals with type 1 diabetes, have demonstrated
increases in the absolute risk of diabetic ketoacidosis (DKA). Some cases presented with nearnormal
blood glucose levels or mild hyperglycemia, complicating the recognition/diagnosis of
DKA and potentially delaying treatment. Several SGLT-inhibitors are currently under review by
US Food and Drug Administration (FDA) and European regulatory agencies as an adjunct to
insulin therapy in people with type 1 diabetes. Strategies must be developed and disseminated to
the medical community to mitigate the associated DKA risk.
This consensus report reviews current data regarding SGLT- inhibitor use and provides recommendations to enhance the safety of SGLT-inhibitors in people with type 1 diabetes.
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From the article
Intensive insulin management remains the only option for effective treatment of type 1
diabetes mellitus. However, fear of hypoglycemia (1-3) and weight gain (4) are often barriers to
optimal use of insulin therapy. Consequently, there exists an unmet need and great patient
interest in adjunct therapies of type 1 diabetes to improve glycemic control without increasing
the risk of hypoglycemia and weight gain. Most non-insulin adjunctive therapies approved for
type 2 diabetes are not effective in type 1 diabetes. The only one approved in the US is
pramlintide and it is not used much clinically due to limited efficacy and unfavorable side
effects. One novel strategy studied to improve outcomes in patients with type 1 diabetes is the
addition of sodium glucose cotransporter (SGLT) inhibitors as an adjunct to insulin therapy in
type 1 diabetes.
SGLT-2 inhibitors block the SGLT-2 transporter in the proximal tubule of the kidney
resulting in glycosuria and natriuresis. SGLT-1+2 inhibitors have the additional effect of locally
inhibiting SGLT-1 in the GI tract, delaying absorption of glucose and galactose from the
intestinal tract. The use of SGLT-2 inhibitors in the setting of type 2 diabetes is now
recommended (5) to prevent major adverse cardiovascular events (including mortality and
hospitalizations for heart failure) in patients with established atherosclerotic cardiovascular
disease as well as chronic kidney disease based on the results of the EMPA-REG (6; 7) and
CANVAS trials (8; 9). Similar reductions in hospitalizations for heart failure were seen in
patients at high risk for cardiovascular disease (10).
These agents are being increasingly used off-label in type 1 diabetes management (11)
and are currently under review by the US Food and Drug Administration (FDA) as well as by the
European Medicines Agency (EMA) as an adjunct to insulin therapy in adults with type 1
Decisions from the US and European agencies for sotagliflozin, a SGLT-1+2 inhibitor,
and dapagliflozin, a SGLT-2 inhibitor, are expected in 2019.
It should be noted that ipragliflozin, an SGLT-2 inhibitor currently available in Japan, Korea and Thailand, has recently been approved in Japan for adults with type 1 diabetes to be coadministered with insulin (12).
In the setting of adults with type 1 diabetes, SGLT-inhibitor therapy with dapagliflozin
added to intensified insulin therapy showed moderate efficacy, reducing A1C by ~0.4% (4.4
mmol/mol) at 6 months and ~0.3% (3.3 mmol/mol) at 12 months while demonstrating
improvement in time in range (70-180 mg/dl [3.0-10.0 mmol/L]) by continuous glucose
monitoring (CGM) without an increase in time with hypoglycemia (<70 mg/dl [<3.9 mmol/L])
(13-15). Importantly, this benefit was demonstrated in the setting of blinded studies where
patients treated with both SGLT-inhibitor and placebo had ongoing protocol-driven adjustments
of basal and bolus therapy (16).This improvement in glycemia was achieved in the context of a
~11.0% reduction of total daily insulin dose compared to ~8.0% reduction in the placebo group
(p<0.0001) (16).Interestingly, although no substantial dose dependency to the improvement in
glycemic control was observed, weight change did seem to be somewhat dose dependent (16).
Moderate weight loss (~3.2% at 6 months and ~3.5% at 12 months) with the SGLT-inhibitor as
compared to placebo (~0.1%) was observed (16).
The EASE Phase 3 program included 2 double-blind, placebo-controlled trials
investigating the efficacy and safety of empagliflozin as an adjunct to insulin therapy in adults
with type 1 diabetes (17). Significant reductions in A1C were observed in the three
empagliflozin doses studied: 2.5 mg (−0.28% [3.1 mmol/mol]), 10 mg (−0.54% [5.9
mmol/mol]),) and 25 mg (−0.53% [5.8 mmol/mol]), all p<0.0001, with no increase in
hypoglycemia. Significant reductions in weight, blood pressure and total daily insulin dose were
also observed in the empagliflozin treatment groups. Treatment with sotagliflozin (SGLT-1+2
inhibitor) showed similar improvements in A1C, weight loss, systolic blood pressure, and
reductions in total daily insulin dose but also with reductions in systolic blood pressure (18).
In studies that reported patient reported outcomes or quality of life assessment, there were
significant benefits associated with SGLT inhibition in the setting of type 1 diabetes (19; 20).
Results regarding the incidence or rate of severe hypoglycemia were somewhat mixed, but in
general, the expected increase in severe hypoglycemia in the context of the greater reduction in
A1C with the SGLT-inhibitor was not observed. Continuous glucose monitoring further revealed
improved time in range, generally ~3 hours a day, with all three SGLT-inhibitors (sotagliflozin,
dapagliflozin, empagliflozin) studied at the highest dose, without an increase in time in
Although SGLT-inhibitor therapy has shown improvements in glycemic control, weight
loss and other risk reductions, current studies have reported a significant increase in the risk for
DKA (13-15; 17; 21; 22) which appears to be dose dependent (13-15; 17).
The definitions for probable/possible/potential events are very different between the programs
and the trigger event identification process to identify potential events differed. Therefore, a
direct comparison between the programs is difficult. Importantly, some study
participants who experienced DKA presented with only slightly elevated glucose levels, a
condition referred to as euglycemic DKA (euDKA). In the setting of euDKA, the usual clinical
alert provided by hyperglycemia is absent and many case reports have demonstrated substantial
delays in recognition, diagnosis and treatment.
In June 2018, the International Conference on Advanced Technologies & Treatment for
Diabetes (ATTD) convened a consensus conference with an international panel of 26 physicians
and researchers with expertise in using SGLT-inhibitor therapy to develop strategies to mitigate
DKA and euDKA risk. Following the conference, twenty-four conference participants completed
an online survey to better understand areas of consensus and areas of disagreement including
appropriate cut-points for DKA diagnosis, risk factors, patient selection, and patient
management. This review summarizes our consensus recommendations and key considerations
for the safe use of SGLT-inhibitors in patients with type 1 diabetes. Scientific questions
requiring further research were also identified.
Ketoacidosis with SGLT-inhibitors in type 1 diabetes: possible mechanisms
Several mechanisms likely operate to predispose individuals with type 1 diabetes to
develop ketosis (increased levels of ß-hydroxybutyrate and acetoacetate) and ketoacidosis in the
setting of SGLT-inhibitor therapy. The reduction of total daily insulin doses and particularly
basal insulin when treating patients with an SGLT-inhibitor may cause failure to suppress
lipolysis and ketogenesis even if blood glucose levels do not rise (23; 24). SGLT-inhibitors are
associated with an increase in glucagon, perhaps as a result of urinary glucose loss or through
direct action upon pancreatic alpha-cells, which increases lipolysis and ketogenesis (25; 26). The
balance of glucagon and insulin are critical to regulating these metabolic pathways (23; 27-29). It
has also been proposed that SGLT-inhibitors decrease renal clearance of ketone bodies (23).
Starvation ketosis, which is also mediated by reduced insulin levels and increased
glucagon levels, can occur in non-diabetic individuals with prolonged periods of fasting or very
low carbohydrate diets (often referred to as ketogenic diets) and is accelerated by physical
activity, physiological stress (e.g., infection or pregnancy) and alcohol consumption. SGLT
inhibition, by increasing urinary glucose loses, may be causing a pharmacologic push towards
ketosis, particularly when the behavioral and physiological factors mentioned are present (23;
30). Readers are referred elsewhere for comprehensive review of the physiology and
pharmacology of this system (23; 31).
The spectrum of ketosis (measured ketones in the blood or urine) to ketoacidosis (ketosis
associated with anion-gap metabolic acidosis) is quite broad involving an approximately 10-fold
range of ketone body concentration. The increase in ketonemia and ketonuria is not due to
reduced renal ketone excretion (9) unless there is severe dehydration (hence, frequently with
DKA is usually associated with hyperglycemia in the setting of diabetes and serum
ketones >3.0 mmol/L. Similar to DKA, the development of euglycemic DKA (euDKA) is
characterized by anion-gap metabolic acidosis, ketonemia and ketonuria but with normal or
modestly elevated blood glucose levels (<250 mg/dL [13.9 mmol/L]) (31; 32). As such, patients
can present with full-blown DKA but with glucose levels <250 mg/dL (<13.9 mmol/L). Table 1
lists the levels of serum/urine ketones that are associated with concern and what should be done
in response to the values.
Approaches to Prevention of DKA Related to SGLT-Inhibitor Therapy
Selection of appropriate patients for SGLT- inhibitor therapy is critical to minimizing
DKA risk. The paramount criterion for patient selection is presentation with normal ketone levels
(<0.6 mmol/L blood ketones; negative urine ketones). However, the risk factors associated with
each patient’s lifestyle/behaviors (Table 2) and willingness/ability to follow prescribed regimens
for monitoring ketones and responding appropriately to elevated ketone levels when present must
also be considered (Table 3).
As a general guideline, SGLT-inhibitor therapy should not be used in patients using lowcarbohydrate
or ketogenic diets as, anecdotally, they seem to be at increased risk of adverse
ketosis effects and certainly create a diagnostic dilemma in evaluating the clinical significance of
ketosis. Also, with regards to diet, patients who skip meals and/or consume excessive alcohol
seem to be at increased risk. Patients who use an insulin pump are also at increased risk due to
the possibility of pump or insulin infusion set malfunction. Patients with type 1 diabetes who
miss insulin doses, have recurrent episodes of DKA or experience prolonged significant
hyperglycemia (particularly >350 mg/dl) and/or display low engagement with their diabetes
regimen are certainly at high risk of DKA in the setting of SGLT-inhibitor therapy. However,
these patients may be considered candidates if they can demonstrate the sustained necessary
changes in lifestyle and self-management behaviors, as well as monitor their capillary/urine
Because adequate studies of SGLT inhibitors have not been performed in pregnant
women, SGLT2 inhibitors should not be used in pregnant women with type 1 diabetes as
pregnancy is associated with an increased risk of ketoacidosis which is associated with a high
risk of fetal mortality (33). No data are currently available for use of SGLT-inhibitor therapy in
children and youth with type 1 diabetes <18 years of age.
Insulin dose adjustments
When initiating SGLT-inhibitor therapy in individuals with type 1 diabetes, insulin must
be reduced cautiously in order to prevent ketosis and DKA. In clinical trials of SGLT-2
inhibitors, the proportional dose reductions seen for basal and bolus insulin were similar (13; 14)
or primarily in basal insulin doses (34). However, when using sotagliflozin, the dose reductions
observed in the clinical trials were largely in the prandial or meal associated insulin (18).
Therefore, the clinician needs to individualize such reductions for each patient based primarily
on degree of hyperglycemia as well as the specific SGLT-inhibitor used.
In patients who are relatively well controlled (A1C <7.5% [<58 mmol/mol]), 10-20%
reductions in insulin doses, accompanied by frequent blood glucose monitoring or CGM, and
rapid readjustment with healthcare provider input is recommended. Some patients may need to
decrease their carbohydrate intake in order to accommodate the reduced insulin dose as long as
ketone levels do not rise. Others may need to increase their carbohydrate intake in order to
maintain adequate exogenous insulin levels to prevent ketosis. Adjustments in insulin doses
should be made at least every 24-48 hours initially.
For less well-controlled patients (A1C ≥7.5% [≥58 mmol/mol]), only slight or no
reductions in prandial and basal insulin may be needed. Determination of which insulin doses
should be reduced should be based on detailed assessment of blood glucose profiles or,
preferably, CGM data as well as hypoglycemia history and awareness.
Initiation and dosing of SGLT-inhibitors
As discussed, blood ketone (ß-hydroxybutyrate) levels should be <0.6 mmol/L prior to
initiating SGLT-inhibitor therapy. If blood ketones are ≥0.6 mmol/L, additional baseline blood
ketone values should be obtained to determine whether the elevated ketones are normal for the
patient (due to lifestyle factors) or an indication of chronic inadequate insulin coverage in the
We recommend that SGLT-inhibitor therapy be initiated at the lowest dose available.
Some suggest even splitting tablets for the currently marketed SGLT2 inhibitors to get to lower
than marketed doses. Patients who had a good experience with low dose SGLT-inhibitor therapy
could be considered for dose escalation based on clinical response.
As observed in clinical trials, lower doses of SGLT-inhibitors are associated with
reasonable efficacy and lower risks of DKA (13; 14). Specifically, the EASE program included a
lower dose (i.e. empagliflozin 2.5 mg) which is not currently available in addition to the doses
approved for use in patients with type 2 diabetes (i.e. empagliflozin 10 and 25 mg) (17). The
ketoacidosis rate was comparable between empagliflozin 2.5 mg and placebo but increased with
10 mg and 25 mg. These data suggest that SGLT2 inhibitor dose selection itself is an important
factor in terms of DKA risk mitigation.
Ketone testing is required because development of euDKA cannot be detected by glucose
monitoring. Although laboratory testing is the most precise method for ß-hydroxybutyrate levels
in clinical settings (35), self-testing via a blood ketone meter or urine testing, is sufficient for
patient use in detecting ketosis and early development of DKA -- blood ketone (ßhydroxybutyrate)
concentrations >0.6 mmol/L or trace (or greater) urine ketones (acetoacetate).
We recommend patient self-measurement of capillary blood ketones, specifically ßhydroxybutyrate
(the most prevalent ketone body) as a matter of routine in assessing the
metabolic state of patients with type 1 diabetes treated with SGLT-inhibitors (36-40). In patients
who cannot afford or do not have access to capillary blood ketone measurements, urine ketone
measurements are acceptable. However, it must be recognized that the urine test only measures
acetoacetate, not ß-hydroxybutyrate, and estimation of urine ketones will be an average of the
concentration within the urine held in the bladder since the last void (41). Moreover, urine output
is frequently low in patients with DKA due to dehydration, and it may take several hours until
urine is produced again, which may delay appropriate treatment (41). Because β-hydroxybutyrate
is oxidized to acetoacetate with treatment of DKA, urine ketone readings will rise with treatment
even if blood β-hydroxybutyrate concentrations are dropping (41). The paradoxical rise in urine
ketones could give the false impression that the DKA is not resolving.
Patients should not rely on a single ketone measurement for definitive determination of
their metabolic state. In patients with elevated ketones, rechecking glucose and ketone
measurements every 1-3 hours should be performed to ensure resolution of ketonemia/ketonuria.
Symptoms of ketosis do not correlate well with ketone levels, which can increase rapidly.
Currently, there is no evidence to support specific testing regimens. However, it is the
consensus of the group that ketone testing frequency should be individualized, according to the
patient's lifestyle and/or risk factors after initiating therapy. However, for all patients, we
recommend that ketones be measured with any symptoms consistent with DKA including
malaise, fatigue, nausea, and vomiting. Ketones should also be measured with changes in diet,
activity or insulin dose as well as for concomitant events such as infection, dehydration, surgery,
injury, pump occlusion/malfunction, or stress. It should be noted that treatment with SGLTPage
inhibitors in patients using insulin pumps with automated features including low glucose insulin
suspend and hybrid closed loop has not been well studied. Ketones should be measured
repetitively for as long as symptoms persist, or stressors remain. Random or periodic
measurement of ketones is also recommended to ensure that ketone testing supplies are readily
available and not expired.
Holding or discontinuing SGLT-inhibitor therapy
Any nausea, vomiting or abdominal discomfort should prompt discontinuation of SGLTinhibitor
therapy and evaluation of ketosis. SGLT-inhibitor therapy should be withheld
immediately if the patient is hospitalized, acutely ill or unable to eat and drink normally. SGLTinhibitors
should be withheld or discontinued prior to any medical procedure (ideally for 3 days),
particularly if they will be reducing food intake or if they will not be allowed to eat or drink for
some time before and after the procedure.
For patients who are switching the type of insulin therapy (e.g., injections to insulin
pump therapy) or from manual mode to automode on an automated insulin delivery (AID)
system, it is prudent that they hold their SGLT-inhibitor until their insulin doses are adjusted,
blood glucose is controlled, and ketone levels are normal.
When elevated ketones are present, patients should be instructed to first discontinue
SGLT- inhibitor therapy until ketones are back to baseline. Treatment must be initiated swiftly
once elevated ketones are identified in order to avoid DKA and potential hospitalization. The key
to treatment of ketosis is for patients to inject insulin and consume carbohydrates, as well as
maintain adequate hydration. Even if the patient is on an insulin pump, the first step in treatment,
insulin, it is often best done by injection. If on insulin pump therapy, it is very important for
patients to begin to trouble shoot the pump and give insulin by injection until they are sure that
the insulin pump is delivering insulin and any pump or infusion set issues are resolved.
If the symptoms and/or ketones are worsening, the patient should seek immediate
medical assistance. Whether or not to send a patient for further medical evaluation is a very
individual decision and may need to occur sooner in the presence of additional co-morbidities,
such as cardiovascular disease or pneumonia. If patients go to the emergency department or an
urgent care center, they should inform the medical personnel that they have type 1 diabetes and
are on an SGLT-inhibitor, which means they can have DKA with a relatively normal glucose
level. Patients should have an evaluation that includes measurements of capillary/venous pH,
blood bicarbonate, anion gap, and blood ketones (ß-hydroxybutyrate).
Patient and clinician education
All patients should receive thorough instruction in DKA risk factors, ketone monitoring
and treatment protocols. This is especially important for patients for whom administration of
both insulin and carbohydrates is counter-intuitive when glucose levels are only slightly
Patients should also be instructed about anticipated situations where they may wish to
hold their SGLT-inhibitor. This includes such events as increased physical activity, situations
where they may become dehydrated or they choose to alter their dietary intake or consume more
alcohol. Therefore, it is important that patients become familiar with how these factors impact
their ketone levels. Importantly, patients should be empowered to make decisions regarding
whether or not to stop their SGLT-inhibitor. Holding it for a day, if in doubt, is prudent and
should not cause significant metabolic issues.
All patients treated with SGLT-inhibitor therapy should be provided with educational
materials (e.g., wallet cards, refrigerator magnets, etc.), which can serve as reminders regarding
risk factors and provide "quick reference" resources for treatment.
Use of SGLT-inhibitor therapy in people with type 1 diabetes should be limited to
practitioners well-versed in the principles reviewed herein. In medical settings, DKA should be
considered in all patients taking SGLT-inhibitors who present with typical symptoms of DKA
even when glucose levels are normal. Because current guidelines for treatment identify DKA as
a hyperglycemic emergency, it is important that emergency departments are made aware that
DKA can present without overtly elevated glucose levels in patients treated with SGLTinhibitors.
This message must be part of all professional education initiatives. Educational
components of a risk mitigation strategy when introducing SGLT- inhibitors for type 1 diabetes
are summarized in Table 4, which includes the STICH protocol for risk mitigation (42).
Because much of the evidence for DKA risk has been garnered from randomized clinical
trials with highly-selected patients, additional research is needed to evaluate the efficacy and
DKA risk of SGLT-inhibitors in larger cohorts of type 1 diabetes patients, using real-world
methodologies. It is also important to develop a better understanding of the apparent dose-
dependent effect in both increased efficacy and increased DKA rates associated with higher
doses of SGLT-inhibitors. Current studies (13; 22) suggest these relationships but were not
Another question that warrants further investigation is whether patients with extremely
elevated A1C levels (>10% [86 mmol/mol]) should receive treatment with SGLT inhibitors. The
5-year follow-up data from the T1D Exchange reported significantly higher (>15%) incidence of
DKA in patients with A1C above 10% (86 mmol/mol) but not treated with an SGLT-inhibitor
(43). Although some believe it is reasonable to recommend this therapy to all patients who are
both willing and able to monitor ketones as prescribed and take the appropriate remedial steps as
needed, some clinicians recommending adjusting insulin therapy to reduce A1C levels prior to
initiation of SGLT-inhibitor treatment, and others recommend not using these agents in anyone
with an A1C >10% [86 mmol/mol]. Additional data are needed to determine whether elevated
A1C is an independent risk factor or not for DKA in patients who are meticulous in their
Developing an evidence base and algorithms to support decisions on reducing insulin
doses should also be a priority for future research. Although the recommendations for insulin
adjustment presented in this report are based on clinical trial experience, clinical judgment and
real-world experience with SGLT-inhibitor therapy, more definitive approaches to matching
each formulation and dosage to reductions in the most appropriate insulin (prandial or basal) and
the degree of reduction that will lessen DKA risk are needed. There is a strong case for a clinical
evaluation of the guidance presented here.
Determination of optimal frequency of ketone monitoring and how and when to respond
to ketone levels that rise above the normal range also remains as questions for further
investigation. Although daily ketone testing may reduce DKA risk, this approach could also lead
to lower adherence if ketone levels are mostly low or zero and the patient does not feel that this
frequency of monitoring is needed (44). Moreover, there is no evidence that daily ketone
monitoring actually prevents DKA; available clinical trials in type 1 diabetes patients did not use
protocols that included daily monitoring of ketones. Cost also represents a major barrier to
increased frequency of ketone monitoring, which could further discourage patients from the
practice. Although urine ketone strips are convenient and much less expensive than blood ketone
meters/strips ($0.20 vs. $2.09 per strip, not including the cost of the blood ketone meter) (45),
the sensitivity and specificity of the urine test for DKA are substantially less than blood ketone
Finally, we recommend evaluation of both patient and clinician education programs and
materials. Although educational interventions for basic DKA prevention in type 1 diabetes
appear to be effective, many patients are not familiar with ketone testing and DKA. It will be
important to evaluate the efficacy and usability of materials specific to SGLT-inhibitor therapy.
At the very least, insulin pump-treated patients must be convinced that a “gluco-centric”
approach” to identifying infusion site problems is not appropriate when receiving adjunctive
therapy with a SGLT-inhibitor.
SGLT-inhibitor therapy is a promising option for adjunctive therapy in the treatment of
type 1 diabetes. Studies in this population have already demonstrated that use of SGLT-inhibitors
confers significant benefits, including improved glycemic control, increased time in range,
improved quality of life measures, and weight loss (13; 18; 22). Moreover, the cardiovascular
and renal benefits demonstrated in the type 2 diabetes trials (7; 8) may be a class effect that
positively impacts all patients regardless of the type of diabetes.
As observed in clinical trials, the rate of DKA in the placebo arm is substantially less
than incidence rates from latest registries where the incidence of DKA with SGLT inhibitor
therapy is relatively low. The increase in the absolute risk in SGLT-inhibitor-treated patients vs
placebo-treated patients was in the range of 4% per year, and in these clinical patients, it was
lower than reported in general practice but still higher than seen with placebo. The potential
benefits of SGLT inhibitors for people with type 1 diabetes appear clinically meaningful. Thus,
strategies for mitigating DKA risk are vital to the adoption and safe use SGLT- inhibitors in all
diabetes populations particularly those requiring insulin. The consensus recommendations
presented in this report are based on current evidence from clinical trials and our expertise and
experience using SGLT-inhibitors with our type 1 diabetes patients. Our goal is to provide a
starting point for the safe use of SGLT-inhibitor therapy in this population and to encourage
additional investigations that will provide more comprehensive, evidence-based- guidance for
clinicians and patients.
Christopher G. Parkin and Martin J. Kurian performed the literature search. Thomas Danne, Anne L. Peters, John B. Buse, Christopher G. Parkin, Charles M. Alexander, and MartinKurian wrote the initial manuscript draft. All author participated in the consensus conference, contributed to the manuscript content and reviewed and contributed to revisions of the manuscript. Thomas Danne is the guarantor of this work and takes responsibility for the integrity of the information and recommendations.
Table 3. Patient criteria for SGLT-inhibitor therapy
>18 years of age
Adherent to prescribed diabetes regimen
Willing/able to perform all prescribed diabetes self-management tasks
Performs blood glucose monitoring or uses CGM as prescribed
Willing/able to perform ketone testing as prescribed
Has received education/training in ketone testing and interpreting/acting upon test results
Has access to ketone testing materials
Has immediate access to a clinician if blood or urine ketone levels are elevated
No or moderate use of alcohol; no use of illicit drugs
Not pregnant or wanting to become pregnant
Table 4. Educational components of a risk mitigation strategy when introducing SGLTinhibitors
for type 1 diabetes
All patients initiating SGLT-inhibitor therapy should receive through training/education in
the following areas:
o DKA causes and symptoms
o Euglycemic ketoacidosis
o Importance of ketone monitoring
o Use of ketone monitoring – training in testing procedure, proactive monitoring,
situations when monitoring is indicated
o Treatment protocol for addressing ketosis
o Guidance in when to seek medical attention
All prescribing clinicians should acquire full understanding of the safe use and risks
associated with SGLT-inhibitor therapy:
o Criteria for patient selection -- baseline ketone level, demographic/behavioral
o Training/educational needs of patients – detection (ketone levels, symptoms),
prevention strategies, treatment
o Potential for missed DKA, euDKA
o Treatment strategies – STICH protocol recommended:
STop SGLT-inhibitor treatment for few days
Hydration with a suitable drink (e.g., water or noncaloric athletic drink with
Risk Product labelling, Website
Communication Healthcare Professional Education
Medication Guide, Patient Alert Card*
Table 2. Risk factors for DKA associated with SGLT-inhibitor therapy
Risk Level for DKA Factor
Reduced basal insulin by more than 10 to 20%
Insulin pump or infusion site failure
Reduced or inconsistent carbohydrate intake
Excessive alcohol use
Use of illicit drugs
Acute illness of any sort (viral or bacterial)
Vigorous or prolonged exercise
Reduced prandial insulin dose by more than 10 to 20%
Travel with disruption in usual schedule/insulin regimen
Insulin pump use
Low BMI (<25 kg/m2)
Inconsistent caloric intake
Moderate alcohol use*
* If ketone levels increase from baseline
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