Dr. A. K. Singh; MD, DM (Endo) 🇮🇳

Dr Nitin Kapoor Verified account @KapoorNitinDr · Oct 9, 2023

Glad to be identified among the top 2% of scientists across the world, cited by the University of Stanford. The youngest among the 8 listed from @cmcvelloreoff Indeed an IKIGAI moment.@IndiaESI @Rssdi_official @IdecPune @UniMelb @bakeridi @EndoBrigade @SAFES_endocrine @IMPA_12

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anoop misra @docanoopmisra · Oct 8

Table provided courtesy Dr AK Singh

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CME INDIA Verified account @CMEINDIA1 · Sep 25

GLP-1 Receptor Agonists & Pregnancy — What Does Human Evidence Really Say?
CME INDIA CLINICAL PEARLS

Singh R, Singh A, Singh AK. Human pregnancy outcomes after early glucagon-like peptide-1 receptor agonist exposure:

1. Accidental early exposure ≠ proven teratogenicity.
The most reassuring finding is that no consistent increase in overall major congenital malformations (MCMs) has emerged after inadvertent preconception or early-pregnancy GLP-1RA exposure.

2. But “no signal” does NOT mean “proven safe.”
The evidence remains largely observational, heterogeneous and confounded. Current data argue against a large reproducible teratogenic effect; they do not establish safety for intentional treatment during pregnancy.

3. The evidence base is now much larger than isolated case reports.
The review identified 47 reports, including 17 case reports, 3 case series, 1 pharmacovigilance analysis, 1 regulatory trial-pregnancy dataset, 16 cohort/registry/controlled studies, and 3 systematic reviews with meta-analyses.

4. One of the strongest comparative datasets is reassuring for malformations.
In the multinational Cesta cohort, 938 GLP-1RA-exposed pregnancies in women with T2D were compared with 5,078 insulin-exposed pregnancies. Major congenital malformations were not increased: adjusted RR 0.95 (95% CI 0.72–1.26); first-trimester sensitivity analysis was similarly reassuring (RR 1.03, 95% CI 0.73–1.47).

5. Meta-analyses tell broadly the same story.
One meta-analysis involving 36,963 pregnancies found no increase in MCM versus other antidiabetic agents (OR 1.08, 95% CI 0.86–1.37) or insulin (OR 1.00, 95% CI 0.77–1.28). However, heterogeneity and baseline differences prevent declaring GLP-1RAs pregnancy-safe.

6. Miscarriage remains an area of uncertainty—not established causality.
Signals for spontaneous abortion have appeared in pharmacovigilance and some datasets, but these cannot establish cause and effect. In regulatory trial data, spontaneous abortion was numerically higher among exposed pregnancies, while overall nonviable pregnancy rates were similar between groups.

7. Preeclampsia, prematurity and fetal-growth signals need caution.
Studies have inconsistently reported preeclampsia, preterm birth, altered gestational weight gain, fetal growth abnormalities and renal/genitourinary findings. None currently forms a convincing reproducible drug-specific pattern.

8. The biggest confounder may be the woman—not the molecule.
Women receiving GLP-1RAs commonly have T2D, obesity, PCOS, infertility, hypertension or renal disease—conditions that themselves increase miscarriage, congenital anomaly, hypertensive disorder, prematurity and abnormal fetal-growth risks.

9. Exposure timing matters enormously.
“Used months before conception,” “stopped around conception,” “stopped after a positive pregnancy test,” and “continued through pregnancy” are not biologically equivalent exposures. This is especially relevant to long-acting agents such as semaglutide, dulaglutide and tirzepatide.

10. Accidental exposure is NOT, by itself, an indication for pregnancy termination.
The review supports cautious reassurance rather than automatic termination following inadvertent preconception or early-pregnancy exposure. Appropriate obstetric and metabolic follow-up remains important.

11. Once pregnancy is recognized: STOP the GLP-1RA.
Current evidence supports discontinuing GLP-1RA therapy when pregnancy is identified and promptly transitioning to pregnancy-compatible metabolic therapy. Planned or continued GLP-1RA treatment during pregnancy is not supported by present evidence.

12. Preconception counselling is becoming essential in the GLP-1 era.
Women of reproductive age receiving these agents should be counselled regarding contraception, pregnancy intention, planned discontinuation and transition of therapy. Weight loss may improve ovulation/fertility, particularly in women with obesity/PCOS, making an unplanned pregnancy more plausible.

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Dr Ambrish Mithal Verified account @DrAmbrishMithal · Sep 17

Looking forward to this!

Ahmedabad this Sunday, September 20.

For too long the focus has on been on #weightloss effects of #GLP1 drugs

Recent research reveals the direct benefits of these drugs on organs like the liver, heart, kidneys and brain.

Fascinating area of medicine!

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