Keywords
Ramadan fasting - type 2 diabetes - GLP-1 RA - SGLT2 inhibitors - hyperglycemia -
dehydration - survey
Introduction
Fasting during Ramadan, observed by millions of Muslims worldwide, presents unique
clinical challenges in the management of type 2 diabetes mellitus (T2D). Patients
are exposed to prolonged periods without food or fluid intake, increasing the risk
of hypoglycemia, hyperglycemia, dehydration, and other metabolic complications.[1]
[2]
[3]
Among newer classes of glucose-lowering agents, glucagon-like peptide-1 receptor agonists
(GLP-1 RAs) and sodium-glucose co-transporter 2 (SGLT2) inhibitors have garnered attention
due to their glucose-dependent mechanisms of action and lower risk of hypoglycemia.[4]
[5]
[6]
[7]
[8]
[9]
[10] These properties have made them particularly attractive options during fasting,
when the risk of hypoglycemia must be carefully balanced against the need for effective
glycemic and cardiorenal control.
Recent expert guidelines, including those from the International Diabetes Federation
and the Diabetes and Ramadan (DAR) Alliance, endorse the use of GLP-1 RAs and SGLT2
inhibitors during Ramadan, highlighting their favorable safety profiles and benefits
beyond glycemic control.[11]
[12]
[13]
[14]
[15] Several other groups produced literature reviews, consensus statements, and guidance
specific to GLP-1 RAs and SGLT2 inhibitors.[16]
[17]
[18] However, some physicians remain hesitant to initiate or adjust these therapies during
Ramadan due to concerns about dehydration and the rare occurrence of euglycemic diabetic
ketoacidosis with SGLT2 inhibitors, as well as gastrointestinal side effects with
GLP-1 RAs.[16]
[17]
[18]
[19] In particular, the timing of drug initiation, dose titration, and patient counseling
strategies remain inconsistent and may differ between endocrinologists and nonspecialists.
This disconnect between evidence-based recommendations and real-world prescribing
practices warrants further investigation. Earlier, smaller surveys revealed a gradual
shift in physicians' comfort levels with these agents during Ramadan, especially SGLT2
inhibitors, but data remain limited in scope and regional representation.[20]
[21]
Although clinical studies and expert recommendations support their safety during fasting,
there are limited data on how these agents are used in real-world practice. The lag
of real-world adoption behind guidelines is well-recognized. Both systemic or clinician-level
barriers could be contributory. These may include limited access to updated training,
uncertainty about fasting-related risks, or lack of structured decision-making tools
for Ramadan-specific care.
To address these gaps, this study explores physicians' real-world perceptions, prescribing
behavior, and clinical decision-making regarding GLP-1 RAs and SGLT2 inhibitors during
Ramadan. Particular attention is given to the differences between endocrinologists
and non-endocrinologists to identify practice variation, areas of hesitancy, and opportunities
for targeted intervention.
Materials and Methods
Objective
The study aimed to (1) explore physicians' perceptions of the safety of these newer
classes of antidiabetic drugs during Ramadan, (2) document availability and access
to these medications in their health care settings, (3) establish their initiation,
titration, and dosing practices in relation to Ramadan, and (4) assess their counseling
practices and patient support strategies in this context. A prespecified subgroup
comparison between endocrinologists and non-endocrinologists was also conducted to
evaluate differences in prescribing patterns, timing of initiation, and safety-related
counseling approaches.
Target Population
The target population was identified from a list of electronic mail addresses, pooled
from participants in various activities conducted by the DAR International Alliance.
This included attendees of conferences, contributors to guideline initiatives, and
participants in previous surveys or educational campaigns.
A few questions were added to the survey to delineate the demographic and professional
profiles of the respondents and their practice settings. While the sample was diverse,
it may reflect a population more engaged with diabetes care and Ramadan-specific education,
which could introduce a degree of selection bias.
Survey Management
A Web-based commercial survey management service (SurveyMonkey Inc., San Mateo, California,
United States; www.surveymonkey.com) was utilized. All participants received an initial e-mail or a link, which explained
the rationale of the survey and what was required from consenting respondents, followed
by two subsequent reminder e-mails during the study period. Each message included
the principal investigator's affiliations and contact details, as well as a unique
email-specific electronic link to the questionnaire. The survey Web site was open
for 2 weeks, from December 19, 2024 to January 1, 2025. Survey responses were collected
and stored electronically for anonymous analysis.
In addition to direct emails, the survey link was also distributed through professional
WhatsApp groups, physician networks, and social media platforms affiliated with the
DAR Alliance to increase geographic reach and physician engagement.
Survey Questionnaire
The first part captured the professional and demographic profiles of the respondents.
The survey questions were constructed as multiple-choice questions covering knowledge,
attitudes, and practices regarding the use of GLP-1 RAs and SGLT2 inhibitors before,
during, and after Ramadan fasting (RF). It was based on the available literature,
clinical practice, and available guidelines.[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18] The survey was drafted by one author (B.A.) and developed further through several
rounds of communications between the authors.
The content validity was ensured by expert review, iterative revisions, and alignment
with guideline-recommended practices.
The questionnaire did not specifically capture patient-level clinical parameters such
as baseline A1c, renal function, or comorbidities. Similarly, the survey did not explore
detailed strategies for co-managing other antidiabetic medications (e.g., insulin,
sulfonylureas, diuretics), nor did it include structured questions on specific nutritional
counseling content such as guidance on fatty Iftar meals. These are acknowledged limitations
and discussed accordingly.
Data Analysis
The survey software tools were used to calculate summary statistics for responses
to each question. As not all participants may have answered all the questions, the
proportion of respondents providing a given answer was calculated individually, using
the number of respondents for that question as the denominator. Subgroup analysis
was performed between endocrinologists and non-endocrinologists using chi-square tests.
Where appropriate, confidence intervals and effect sizes were calculated to assess
the strength and clinical relevance of observed differences. We refrained from undertaking
further subgroup analyses to avoid confounding factors resulting from differences
in access and economic factors. All statistical tests were exploratory and intended
to identify trends rather than establish causality.
Results
Demographic and Professional Profiles of Respondents
The total number of responses was 939, coming from diverse geographical areas, with
the majority originating from the Middle East and North Africa (MENA) and South East
Asia regions ([Fig. 1A]). Most respondents represented endocrinology (40%), followed by internal medicine
and general practice ([Fig. 1B]). More respondents practiced in public health care facilities than in private practice
([Fig. 1C]). The number of T2D patients likely to fast varied, but over 50% of respondents
reported seeing more than 50 individuals with diabetes, who are likely to fast ([Fig. 1D]). This sample reflects a wide physician base across health care systems, though
the predominance of endocrinologists and public-sector clinicians may introduce a
degree of specialization bias that limits extrapolation to broader, less-specialized
practice settings.
Fig. 1
(A–D) Respondents' geographical distribution, clinical specialty, practice setting, and
number of people with diabetes who are likely to fast during Ramadan.
Drug Availability
There was less availability and access to GLP-1 RA ([Fig. 2A]) than for SGLT2 inhibitors ([Fig. 2B]). GLP-1 RA was readily available to 64.6% of respondents, compared with SGLT2 inhibitors,
which were readily available to 78.59% of respondents ([Fig. 2B]). Correspondingly, the limited availability of GLP-1 RA was greater than SGLT2 inhibitors
(33.65% vs. 20.77%). Only an extreme minority reported a lack of either class.
Fig. 2
(A, B) Reported availability and accessibility of GLP-1 RA and SGLT-2 inhibitors in the
respondents' clinical practice settings.
Drug Initiation, Titration, and Dosing
Respondents' practices regarding initiation, titration, and typical dosing during
RF are presented for GLP-1 RA in [Fig. 3] and for SGLT2 inhibitors in [Fig. 4].
Fig. 3 Respondents' practices regarding GLP-1 RA use during Ramadan: initiation (A), titration protocols (B), and typical dosing adjustments (C).
Fig. 4 Respondents' practices regarding SGLT-2 inhibitor use during Ramadan: initiation
(A), titration protocols (B), and typical dosing adjustments (C).
For GLP-1 RA initiation, most physicians started GLP-1 RAs before Ramadan, often several
weeks in advance. For instance, over 70% would not initiate GLP-1 RAs in the 4 weeks
leading up to Ramadan, and approximately 50% follow the same titration protocol during
Ramadan, while 70% do not change the dose of GLP-1 RAs during this period ([Fig. 3A], [B]). Adjustments were made to manage gastrointestinal side effects ([Fig. 3C]).
Similarly, for SGLT2 inhibitors, three-quarters of respondents would not initiate
SGLT2 inhibitors within 4 weeks before Ramadan. Almost 50% of respondents initiate
during fasting if necessary ([Fig. 4A], [B]). The majority (72.1%) maintain the pre Ramadan dose ([Fig. 4C]).
Prevention and Management of Adverse Events
For GLP-1 RA, [Fig. 5] illustrates counselling strategies for the prevention and management of adverse
events and complications before and during Ramadan. The preferred timing for GLP-1
RA injections during Ramadan was in the evening or after Iftar. The main counseling
points for GLP-1 RAs during Ramadan were the management of worsening nausea or vomiting
on GLP-1 RAs during Ramadan. Management approaches for nausea and/or vomiting, including
symptomatic treatment or temporary dose adjustments, were common. The key counseling
points included reassurance about safety, monitoring symptoms, hydration, and the
timing of administration. Most physicians provided anticipatory guidance, emphasizing
reassurance about medication safety, active symptom monitoring, adequate hydration
during nonfasting hours, and timing administration with meals to reduce gastrointestinal
intolerance.
Fig. 5
(A–C) Counselling strategies for prevention and management of adverse events and complications
related to GLP-1 RA therapy during Ramadan.
For SGLT2 inhibitors, [Fig. 6] illustrates the counseling strategies for the prevention and management of adverse
events and complications associated with SGLT-2 inhibitors before and during Ramadan.
For the prevention of dehydration, respondents emphasized the importance of hydration
during nonfasting hours and adjusting doses accordingly. Most respondents recommended
administering the medication at Iftar or in the evening. Key counseling points included
the importance of fluid intake, recognizing signs of urinary frequency or infection,
understanding the symptoms of volume depletion, and being reassured of the overall
safety profile when used appropriately. However, as noted in reviewer feedback, more
detailed counseling—such as specific dietary modifications (e.g., avoiding excessively
salty or caffeinated foods)—was not systematically assessed in the survey, representing
an area for future research.
Fig. 6
(A–C) Counselling strategies for prevention and management of adverse events and complications
related to SGLT-2 inhibitor therapy during Ramadan.
Specialist Comparisons
Endocrinologists were more consistent in early initiation of both drug classes before
Ramadan, making structured dose adjustments, and offering comprehensive counseling.
On the other hand, non-endocrinologists showed more variation and a tendency toward
cautious initiation or avoidance. Specifically, endocrinologists were significantly
more likely to initiate treatment ≥4 weeks before Ramadan, adhere to titration protocols,
and provide counseling tailored to side-effect profiles and fasting-related risks.
In contrast, nonspecialists often avoided initiating these agents near or during Ramadan
and reported less structured counseling approaches. These differences underscore the
potential impact of specialty training and familiarity with fasting-specific guidelines
on real-world prescribing behavior.
Discussion
The findings of this survey revealed a high level of awareness and clinical responsibility
among physicians managing patients with T2D during RF. Most respondents demonstrated
an understanding of the unique metabolic challenges posed by prolonged fasting and
showed prudence in prescribing decisions related to GLP-1 RAs and SGLT2 inhibitors.
Predictably, endocrinologists were more consistent in aligning their clinical practices
with current evidence and expert recommendations, particularly in the early initiation
of therapy and in delivering structured patient counseling. However, considerable
variation in practice was noted, especially among nonspecialists and general practitioners.
This variability may be due to differences in training, access to recent guidelines,
or concerns about adverse events.
Importantly, such variation may have direct implications for patient safety, medication
adherence, and fasting continuity—particularly if clinical inertia or hesitancy leads
to underutilization of therapies known to be safe and effective.
These results support the ongoing need for targeted continuing medical education,
cross-disciplinary engagement, and culturally sensitive decision-making tools to bridge
the gap between evidence-based practice and real-world application.
A substantial body of evidence supports the use of GLP-1 RAs and SGLT2 inhibitors
during RF in patients with T2D in various contexts.[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31] These agents are favored for their glucose-dependent mechanisms, which reduce the
risk of fasting-induced hypoglycemia—a central concern during prolonged periods of
abstinence from food and fluid.
GLP-1 RAs, such as liraglutide, lixisenatide, and oral semaglutide, effectively lower
HbA1c and weight with minimal risk of hypoglycemia when administered properly.[21]
[22]
[23]
[24] Similarly, SGLT2 inhibitors, including dapagliflozin, empagliflozin, ertugliflozin,
and canagliflozin, offer glycemic and weight benefits, as well as cardiovascular and
renal protection in selected populations.[25]
[26]
[27]
[28]
[29]
[30]
[31] These benefits make them ideal candidates for fasting patients, provided that therapy
is introduced with appropriate monitoring and patient education.
Although concerns such as dehydration and rare events like euglycemic diabetic ketoacidosis
persist, these can often be mitigated, through patient selection, adequate hydration
during nonfasting hours, and appropriate monitoring. Both drug classes are now considered
suitable for many patients observing Ramadan, as reflected in international guidelines.[11]
[12]
[13]
[14]
[15]
Nevertheless, the survey findings confirm that real-world prescribing continues to
vary significantly—often driven by physician caution rather than patient-specific
contraindications. This highlights an ongoing disconnect between evidence-based safety
profiles and practical decision-making, especially among nonspecialists who may be
less familiar with fasting-focused management strategies.
The present survey revealed that GLP-1 RAs were readily available to 64.6% of respondents,
compared with SGLT2 inhibitors, which were readily available to 78.59% of respondents;
this corresponds to greater restricted access to GLP-1 RAs than SGLT2 inhibitors (33.65%
vs. 20.77%). These findings reflect the cost difference between the two classes. Only
a very small minority reported a complete lack of either class; yet, this likely reflects
institutional or market-level access rather than individual patient affordability
or prescribing feasibility.
Notably, the uptake of GLP-1 RAs in the real-world data from the DAR Global Survey
2022 remained limited despite their inclusion in recent guidelines, suggesting cost
and logistical factors continue to constrain broader use.[32]
The present survey revealed that over 75% of respondents avoided starting GLP-1 RAs
in the 4 weeks leading up to Ramadan, reflecting concerns about gastrointestinal side
effects and the time required for dose titration despite the reassuring recommendations.[10]
[11]
[12]
[13]
[14]
[15] Similarly, most respondents initiated SGLT2 inhibitors well before Ramadan, with
more than 70% maintaining the pre-Ramadan dose throughout the fasting period, similar
to earlier surveys.[19]
[20] These findings suggest an overcautious prescribing behavior aiming at minimizing
adverse events and allowing patients to adapt to therapy before initiating the fast.
While this approach reflects clinical prudence, it may also limit timely access to
these beneficial agents, particularly in patients newly diagnosed close to Ramadan.
Nonetheless, there are adequate reassuring data on the minimal risk of dehydration
and renal injury,[29]
[30]
[31] ketonemia,[27]
[31] and hypoglycemia,[25]
[27] as well as overall tolerability.[28] Translating this growing body of evidence into confident prescribing remains an
area for educational reinforcement.
Participating physicians could recognize and manage side effects associated with GLP-1
RA and SGLT2 inhibitors during Ramadan. Their strategies suggest a proactive and individualized
approach, particularly in addressing gastrointestinal symptoms related to GLP-1 RAs
and hydration concerns associated with SGLT2 inhibitors. Although rare, the risk of
euglycemic diabetic ketoacidosis with SGLT2 inhibitors was acknowledged, with prevention
centered on reinforcing hydration and symptom awareness.[33]
This reflects a reassuring degree of clinical vigilance and alignment with best practices.
These responses demonstrate consistency with current safety recommendations and underscore
the importance of anticipatory guidance in mitigating risks associated with fasting.[11]
[12]
[13]
[14]
[15] However, as noted by reviewers, counseling on other relevant aspects—such as meal
composition or co-medication adjustments—was not captured in detail, signaling an
opportunity for future structured assessment.
Effective patient counseling is a central component of safe prescribing during Ramadan.[11]
[12]
[13]
[14]
[15] It is particularly crucial when involving medications that may carry a risk of side
effects relevant to RF, where safety is the overriding principle for individualized
risk assessment and personalized care.[34]
A high consistency is observed in the responses. For example, concerning GLP-1 RA,
a high proportion (85%) advised taking it at Iftar or during eating hours. Counseling
is usually related to gastrointestinal side effects, and most physicians advise dose
reduction for those with worsening nausea or vomiting.[18]
[21] On the other hand, to mitigate the potential side effects of SGLT inhibitors, most
respondents acknowledged the impact on fluid balance. They counseled patients appropriately
on the timing of taking the medications and the importance of maintaining adequate
hydration in line with the widely recommended expert consensus.[16]
[17] These responses highlight physicians' attentiveness to fasting-specific risks and
their adaptation of counseling strategies to the pharmacologic profiles of each agent.
However, more structured guidance and training may be needed to ensure consistent
delivery of advice on related factors such as dietary triggers and co-administered
medications.
A few noteworthy factors limit the study. The self-reported perceptions and attitudes
may not fully reflect actual clinical practice, as respondents might overestimate
adherence to guidelines or best practices. This introduces the potential for reporting
bias and underscores the need for complementary audit-based quality improvement initiatives
that assess real prescribing behavior and patient outcomes. Nonetheless, the survey
provides valuable insight into clinician knowledge, practice variation, and areas
of hesitancy. Although the total number of participants is remarkable for a cross-sectional
survey, disproportionate representation is evident, with a predominance of respondents
from the Gulf and MENA regions. This regional skew may limit generalizability, as
economic disparities, medication availability, and health care infrastructure could
differ significantly in other settings. Longer recruitment periods and the introduction
of geographic quotas in future surveys may help mitigate this imbalance. Additionally,
selection bias is likely, as the sample was drawn from a database of clinicians engaged
in Ramadan-focused education and initiatives, potentially overrepresenting those who
are guideline-aware and actively interested in this field.
Conclusion
GLP-1 RAs and SGLT2 inhibitors are widely considered safe for use during Ramadan by
surveyed clinicians. However, notable variability exists in their clinical application,
especially between endocrinologists and other providers. This variation, if unaddressed,
may lead to inconsistent patient care and missed opportunities for optimal metabolic
and cardiorenal protection during fasting.
Future efforts should focus on disseminating evidence-based guidelines and implementing
practical training programs to unify care practices during Ramadan. Further research
should focus on high-risk populations, such as those with advanced comorbidities or
prior complications, and evaluate long-term outcomes of these agents in the fasting
context. Additionally, research is warranted to assess optimal initiation timings
and strategies for dose intensification while maintaining efficacy and safety. Institutional
support for structured, Ramadan-specific education and broader inclusion of nonspecialist
providers in guideline training initiatives may be critical to closing practice gaps.
The current findings support the confident use of these agents during Ramadan, provided
that prescribing is guided by patient assessment, careful timing, structured counseling,
and culturally sensitive care models.
