MANAGEMENT OF

GLUCOCORTICOID - INDUCED
HYPERGLYCEMIA
Preceptor: Mr. Gemechis B (B. Pharm, MSc)

04/07/2024 By Daniel M (B. Pharm, CP -PG2)

 Outline
2

 Overview
 Incidence and Prevalence
 Common Indications for Use of Glucocorticoid
Therapy
 Factors Leading to Increased risk of Hyperglycaemia
with Steroid Therapy
 Management of Steroid Induced Hyperglycemia

By: Daniel M( PG2 Student) 04/07/2024

 Overview
3

 Glucocorticoids are known to have a deleterious effect on

glycemic control
 Steroid treatment is used to treat a variety of conditions
including auto-immune disease (Lupus, RA, IBD, COPD,
chemotherapy protocols etc.)
 Treatment regimes are varied, ranging from acute/short-term
high dose situations to those that are more chronic, and low
dose in nature. By: Daniel M ( PG2 Student) 04/07/2024
 Cont’d
4

 Individuals with A1c ≥7 experience worse outcomes

including:
 Higher risks of infection, hospitalization
 Chemo discontinuation or dose reductions
 Higher mortality
 Lower quality of life (QOL) with increased pain intensity
 Risk of HHS non- ketosis syndrome
 Increased BG variability which is associated with increased
risk of CV mortality and fatigue

By: Daniel M( PG2 Student) 04/07/2024

 Incidence and Prevalence
5

 The incidence of GC-induced hyperglycemia is 12%, and the rate

of GC-induced diabetes and hyperglycemia was 18.6% and 32.3%,
respectively.
 The prevalence of glucocorticoid therapy in hospitalized patients
can approach 10%, and these medications can induce
hyperglycemia in 56–86% of these individuals with and without
preexisting diabetes
 If left untreated, this hyperglycemia increases mortality and
By: Daniel M( PG2 Student) 04/07/2024
morbidity risk, e.g., infections and cardiovascular events.
 Common Indications for Use of
Glucocorticoid Therapy
6

Physiological replacement  Adrenal insufficiency, Congenital adrenal hyperplasia

Anti-inflammatory and immunosuppressive effects
Organ system
 Bronchial asthma, Acute exacerbation of COPD,
Respiratory Hypersensitivity pneumonitis, COVID-19, ARDS,
Anaphylaxis, Sarcoidosis, Cystic fibrosis
 Rheumatoid arthritis, SLE, Ankylosing spondylitis,
Rheumatologic
Polymyositis/dermatomyositis, Polyarteritis, Vasculitis
 Acute severe dermatitis, Urticaria/angioedema,
Dermatological
Pemphigus vulgaris
Ophthalmological  Uveitis, Kerato-conjunctivitis, Optic neuritis
 Lymphoma/leukemia, Hemolytic anemia, Idiopathic
Hematological
thrombocytopenic purpura
Endocrine  Sub-acute thyroiditis, Lymphocytic hypophysitis

By: Daniel M( PG2 Student) 04/07/2024

 Cont’d
7

Ulcerative colitis
Gastrointestinal Crohn’s disease
Autoimmune hepatitis
Renal Nephrotic syndrome
Heart, kidney, liver
Organ transplantation
Cornea
Multiple sclerosis
Neurological
Cerebral edema

By: Daniel M( PG2 Student) 04/07/2024

 Factors Leading to Increased risk of
Hyperglycaemia with Steroid Therapy
8

 Pre-existing  Prediabetes (IFG,IGT,

T1DM/T2DM: HbA1c 42-47mmol/mol

 People at increased risk of  Previous hyperglycaemia

DM: with steroid therapy
 Obesity

 Family history of DM

 Prior GDM

 Ethnic minorities,

 PCOS
By: Daniel M( PG2 Student) 04/07/2024
 Risk Factors for Glucocorticoid-Induced
Diabetes Mellitus
9

By: Daniel M( PG2 Student) 04/07/2024

 Mechanisms of Glucocorticoid-Induced Hyperglycemia

10

By: Daniel M( PG2 Student) 04/07/2024

 +Ve Vs. –Ve Effects Of Glucocorticoids
11

By: Daniel M( PG2 Student)

04/07/2024
 Cont’d
12

 Is associated with poor clinical outcomes, including

 Infection,
 Disability after hospital discharge,
 Prolonged hospital stay, and

 Death.
 All admitted patients need to be evaluated for hyperglycemia at
admission with at least 2 capillary blood glucose (CBG)
values (1 pre-meal and 1By:post-meal value).04/07/2024
Daniel M( PG2 Student)
Relative Steroid Potency Equivalents and Duration of Action
Hyperglycemic Effects (hours)
Potency* Relative anti-
Duration of Onset Peak Resolution
Steroid (Equivalent inflammatory
Action
Doses, mg) Activity*

Short Acting
Hydrocortisone 20 8-12 1 1 3 6
Cortisone acetate 25 8-12 0.8 n/a n/a n/a
Intermediate Acting
Prednisone 5 12-36 4 n/a n/a n/a
Prednisolone 5 12-36 4 4 8 12-16
Methylprednisolone 4 12-36 5 4 8 12-16
Long Acting
Dexamethasone 0.75 36-72 30 8 variable 24-36
Betamethasone 0.6 36-72 30 12 variable Up to 72

*N.B. steroid doses are often expressed as prednisone equivalent doses & potency relates to
anti-inflammatory action, relative to hydrocortisone, which may not equate to hyperglycemic
effect
By: Daniel M( PG2 Student) 04/07/2024
13
 Baseline Assessment and Evaluation
14

 Upon admission,
 The patient’s family history,
 Concomitant medication, and
 Clinical status, including illness severity,
 Nutritional status, should be noted and included in day-to-day
decisions concerning insulin doses.
 Random CBG should be performed
 Next, a pre-meal and 2-hour post-meal CBG should be
By: Daniel M( PG2 Student) 04/07/2024
performed with the first major meal in the hospital.
 Cont’d
15

 CBG should be monitored before each meal and, if possible,

after meal as well for at least 2 days for underlying
hyperglycemia if any of the test values are high (i.e., Random
CBG ≥ 180 mg/dL, Pre-meal ≥140 mg/dL, Post-meal ≥180
mg/dL, FPG ≥ 110 mg/dL, HbA1c ≥6.0%).
 Pharmacotherapy should be initiated if any of the test values
meet the glycemic thresholds (i.e. , Random CBG ≥ 250 mg/dL
, Pre-meal ≥150 mg/dL, 2 hours Post meal ≥200 mg/dL).
By: Daniel M( PG2 Student) 04/07/2024
 Management of Steroid Induced
Hyperglycemia
16

 Insulin remains the treatment of choice (it best to manages the

rapid onset of hyperglycemia and can be easily titrated as GC doses
change, and is safe in situations where other agents may be
contraindicated)
 Non-insulin AHAs are unlikely to be as effective in controlling
the hyperglycemia that results from high dose, short-term
and/or cyclical courses of GC therapy where significant titrations
in insulin doses may be required to normalize steroid induced
hyperglycemia. By: Daniel M( PG2 Student) 04/07/2024
 Oral Agents
17

 Are convenient options but have limited primary literature

regarding the efficacy of oral medications
 slow onsets of action and limited titration abilities
 There may be a role for oral medications, especially in the
outpatient management settings
 One of the first therapeutic classes studied for use in people
with steroid-induced hyperglycemia were the
thiazolidinediones.
 Thiazolidinediones work by improving target cell response to
insulin without increasing pancreatic insulin secretion
By: Daniel M( PG2 Student) 04/07/2024
 Glitazons cont’d
18

 Study was done on troglitazone with insulin compared to

insulin alone in participants with long-term steroid-induced
hyperglycemia.
 Troglitazone group showed lower incidence of

hyperglycemia and reduced A1C and PPBG levels.

 However, a clinically significant finding included

participants experiencing a 2.6 kg weight gain in 5 to 8

weeks with troglitazone.
 Their use can be limited in clinical practice because of Slow
onset, risk of weight gain, edema, exacerbation of HF, and
potential elevations in LFT
By: Daniel M( PG2 Student) 04/07/2024
 Metformin
19

 It enhances insulin sensitivity and decreases hepatic

gluconeogenesis.
 In a double blind, placebo-controlled trial, adult participants
with glucocorticoid therapy were treated with metformin or
placebo over 4 weeks.
 Participants in the metformin group had a lower median 2-hour
PPBG level compared to placebo.
 Metformin can be an affordable, minimal risk of hypoglycemia
no effect or a small weight reduction and other adverse events.
 In the inpatient setting, metformin’s role may be restricted
because of renal function and use of contrast media for any
imaging tests. By: Daniel M( PG2 Student) 04/07/2024
 Dipeptidyl peptidase-4 (DPP-4) inhibitors
20

 Saxagliptin and linagliptin, promote enhanced release of

glucose-dependent insulin, inhibit glucagon secretion, and
enhance glucose uptake into peripheral tissues.
 They have beneficial for people receiving intermediate-acting
glucocorticoids in a single morning dose because of effect on
weight (e.g., neutral), immediate onset of action, predominant
effect on PPBG levels, and low risk of hypoglycemia.
 In a study by Ohashi and colleagues in Japan, on people with
CKD, Alogliptin was administered for the treatment of
steroid-induced hyperglycemia.
 Study showed a significant reduced lunchtime PPBG levels 
alogliptin could improve steroid-induced hyperglycemia.
By: Daniel M( PG2 Student) 04/07/2024
 Effects of 6-Month Sitagliptin Treatment on
Metabolic Parameters in Diabetic Patients Taking
Oral Glucocorticoids: A Retrospective Cohort Study
21

 The plasma glucose and HbA1c levels were significantly

reduced by the sitagliptin treatment.
 Furthermore, body weight significantly decreased.

Conclusions:
 Sitagliptin significantly reduced plasma glucose, HbA1c
and body weight.
 Further, sitagliptin was more effective to improve glycemic
control in patients taking glucocorticoids with higher
HbA1c levels.
*J Clin Med Res. 2015 Jun;7(6):479-84
By: Daniel M( PG2 Student) 04/07/2024
 Sulfonylureas
22

 Have been proposed as a treatment option for steroid-induced

hyperglycemia because of their effect on PPBG levels.
 Their long duration of action poses a risk for
hypoglycemia and may be an advantage for people receiving
long-acting steroids such as dexamethasone.
 Take a shorter time to act, so it will help to address acute
hyperglycemia.
By: Daniel M( PG2 Student) 04/07/2024
 Meglitinides
23

 Repaglinide and Nateglinide, have a similar MOA to

sulfonylureas but shorter durations of action.
 A potential disadvantage of meglitinides includes frequency of
administration (e.g., 3 times per day with meals).
 In the inpatient setting, sulfonylureas and/or meglitinides may
be used sparingly because of the potential of hypoglycemia,
specifically with insulin therapy.

By: Daniel M( PG2 Student) 04/07/2024

 Insulin Therapy
24

 General international recommendations, support the use

of insulin to manage steroid-induced DM.
 It offers greatest flexibility (to manage changes in
dosing, food intake, etc.), predictability, and targeted
intervention.
 It does require active patient/family members’ education
and support.
 Initiate treatment if patient experiences persistent
BG>200mg/dl on 2 or more occasions within a 24-hour
period.
By: Daniel M( PG2 Student) 04/07/2024
 Cont’d
25

 Treatment may vary depending on whether people have a

prior history of DM.
 If peoples are known to have diabetes prior to glucocorticoid
initiation, the dose of basal insulin should be increased by 20%.

 In extreme cases, such as people receiving high doses of

steroids with glucose levels consistently above 400 mg/dL,
an insulin infusion is indicated.
By: Daniel M( PG2 Student) 04/07/2024
 Cont’d
26

 For people who are insulin naïve, a prandial scheme may

be best to initiate for glycemic management.
 An initial weight-based dose of 0.1 units per kg per meal is
recommended, which may be modified based on response.
 Basal insulin therapy should be considered when using
high doses of steroids or when hyperglycemia persists
despite pre-prandial corrections.
 Although insulin therapy should be individualized,
institutions, hospitals, and health care systems may have
protocols for treatment of steroid-induced hyperglycemia.
By: Daniel M( PG2 Student) 04/07/2024
 Comparison of Two Protocols in the Management of
Glucocorticoid-induced Hyperglycemia among Hospitalized
Patients: randomized, open-labeled, parallel arm trial
27

 Adult patients who were given glucocorticoid (minimum dose

equivalent to prednisolone 10 mg) in the past 24 h and had 2 h
post meal plasma glucose ≥200 mg/dl were included in the
study. Patients randomized to control group received standard
basal-bolus insulin.
 Fasting, pre-lunch, pre-dinner, bedtime, and pre-meal overall
were all significantly lower in experimental group.
 The experimental group had better glycemic control as
compared to the control group.
 The hypoglycemia event rates were low in both the groups
 Indian J Endocrinol Metab. 2017 Nov-Dec; 21(6): 836-844
By: Daniel M( PG2 Student) 04/07/2024
 Standards of Care in Diabetes—2023
28

 Glucocorticoid type and duration of action must be

considered in determining appropriate treatments.
 Daily-ingested intermediate-acting glucocorticoids such as
prednisone reach peak plasma levels in 4–6 h but have
pharmacologic actions that can last through the day.
 Individuals placed on morning steroid therapy have
disproportionate hyperglycemia during the day but frequently
reach target blood glucose levels overnight regardless of
By: Daniel M( PG2 Student) 04/07/2024
treatment.
 Cont’d
29

 In subjects on once- or twice-daily steroids, administering

intermediate-acting (NPH) insulin is a standard approach.
 For long-acting glucocorticoids such as dexamethasone and
multidose or continuous glucocorticoid use, long-acting
basal insulin may be required to manage fasting blood
glucose levels
 For higher doses of glucocorticoids, increasing doses of
prandial (if eating) and correctional insulin, sometimes as
much as 40–60% or more, are often needed in addition to
basal insulin
By: Daniel M( PG2 Student) 04/07/2024
 Insulin dosing and glycemic outcomes among
steroid-treated hospitalized patients… 2022
30

 A retrospectively study on data collected from the

electronic health records within an academic medical center
from 18,599 patient-days where patients were treated
concurrently with insulin and steroids
 This study found that increasing the ratio of insulin to
steroids was positively associated with improved time in
range; however, there was an increase in hypoglycemia.

*Endocr Pract. 2022 Aug;28(8):774-779

By: Daniel M( PG2 Student) 04/07/2024
 Blood Glucose Targets
31

 In most patients continuing to aim for targets of A1c ≤7%,

FPG <140mg/dl is desirable,
 However, in practice, targeting BGs of 140mg/dl - 180mg/dl,
is reasonable and end of life targets may be liberalized
maintaining an A1c of <8.5%, and BG 140mg/dl - 200mg/dl
while preventing symptomatic hypo/hyperglycemia.

By: Daniel M( PG2 Student) 04/07/2024

 Dose Treatment Regimens and Duration
32

Dose Effects Prednisolone/day Equivalent Dose (mg)

<7.5 mg per day (physiological
Low dose
replacement)
Moderate dose 7.5–30 mg per day
High dose 30 mg per day
Very high dose 100 mg per day
Pulse therapy 250 mg per day for one or few days

Duration

Short-term duration (oral corticosteroids) <21 days

By: Daniel M( PG2 Student) 04/07/2024

 Titrating and Tapering Management
33

 As tapering or discontinuation of GCs occur, concomitant

reduction in in BG lowering medications must occur to avoid
hypoglycemia.
 There is no standard algorithm that encompasses the art &
science of this process.
 It depends upon individual responses to the titration schedule,
type and dose of steroid, and extent of the duration of steroid
treatment
 Patients should be monitor BG 4x/day during periods of
titration (up or down)
 Patients on agents that can cause hypoglycemia should be
counseled to check their BG more frequently for 1-3 days after
04/07/2024
a reduction in GC dose By: Daniel M( PG2 Student)
 Diabetes in Pregnancy & Glucocorticoids
34

 Transient hyperglycemia can present, particularly in

women with pre-existing DM or GDM

 Steroid use in pregnancy is usually, 2 single doses of

betamethasone, to promote fetal lung maturity at birth
in women who may be expecting to deliver prematurely.

By: Daniel M( PG2 Student) 04/07/2024

 Management of pregnant women with
DM on insulin receiving betamethasone
35

Following the first dose of betamethasone

Day 1 Increase the night insulin dose by 25%
Days 2 and 3 Increase all insulin doses by 40%
Day 4 Increase all insulin doses by 20%
Day 5 Increase all insulin doses by 10% to 20%
Gradually taper insulin doses to pre-betamethasone
Days 6 and 7
doses

By: Daniel M( PG2 Student) 04/07/2024

 Acknowledgement
36

 First and for most, I would like to forward My heartfelt

gratitude to the My preceptor; Mr. Gemechis B. (B.
Pharm, MSc in Clinical Pharmacy) for encouraging me
to participate in such kind of activities.
 My dedication thanks also goes to Wallaga University,
Department of Pharmacy for facilitating necessary
materials in preparation of this presentation
By: Daniel M( PG2 Student) 04/07/2024
 Reference
37
1. Shah P, Kalra S, Yadav Y, Deka N, Lathia T, Jacob JJ, et al. Management of
Glucocorticoid-Induced Hyperglycemia. 2022; (February):1577–88
2. Care D, Suppl SS, Brown FM, Bruemmer D, Collins BS, Hilliard ME, et al.
16 . Diabetes Care in the Hospital : Standards of Care in Diabetes — 2023.
2023;46(January):267–78.
3. Longaker L. Evidence-Based Management of Hyperglycemia in the Inpatient
Setting. 2022;(January).
4. Diabetes WW. Managing Steroids & Hyperglycemia : 2023;
5. Roberts A, James J, Dhatariya K. Diabetes UK Position Statements
Management of hyperglycaemia and steroid ( glucocorticoid ) therapy : a
guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care
group. 2018;1011–7.
6. Management of Hyperglycaemia and Steroid (Glucocorticoid) Therapy
Revised January 2023
By: Daniel M( PG2 Student) 04/07/2024
38 By: Daniel M( PG2 Student) 04/07/2024