<img src='https://medicaldialogues.in/h-upload/2025/11/18/309305-surpass-2.webp' /><div class="pasted-from-word-wrapper"><p style="text-align: justify; "><b>Key Summary:</b></p>
<p style="text-align: justify; ">In addition to meeting the
primary objective of noninferiority to semaglutide in type 2 diabetes (T2D),
tirzepatide, at a dose of either 10 mg or 15 mg once weekly, has demonstrated
superiority to semaglutide in this indication. Additionally, tirzepatide was
associated with a clinically and statistically significant reduction in body
weight compared with semaglutide, with achievements of glycated hemoglobin
(HbA1c) close to normoglycemia, with 51% of patients reaching a target HbA1c of
<5.7% at 40 weeks at a tirzepatide dose of 15 mg once weekly.</p>
<p style="text-align: justify; "><b>Introduction:</b></p>
<p style="text-align: justify; ">Tirzepatide (Mounjaro®) is a
highly selective and long-acting dual glucose-dependent insulinotropic
polypeptide (GIP) and glucagonlike peptide-1 (GLP-1) receptor agonist<sup>1</sup>.
GLP-1 receptor agonists act by stimulating insulin secretion, suppressing
glucagon secretion, delaying gastric emptying, decreasing appetite, and
decreasing body weight and have been shown to be effective in the treatment of T2D.<sup>2
</sup>The incretin hormone GIP acts to increase insulin secretion during
hyperglycemia and to increase glucagon levels during fasting and hypoglycemia
conditions.<sup>3</sup></p>
<p style="text-align: justify; ">Tirzepatide is indicated for
the treatment of insufficiently controlled T2D in adults, with recommended
maintenance doses of 5 mg, 10 mg and 15 mg once weekly, administered by
subcutaneous (SC) injection at any time of the day, with or without meals.<sup>1</sup>
In the SURPASS-2 study, patients were randomized to one of three tirzepatide
arms: 5 mg, 10 mg or 15 mg once weekly, or to the active comparator,
semaglutide 1mg once weekly, all on a background of metformin.<sup>4</sup></p>
<p style="text-align: justify; ">Semaglutide is a selective
GLP-1 receptor agonist, approved for the treatment of T2D at a maximum dose of
2 mg injected SC once weekly (at the time of the SURPASS-2 study, the maximum
approved dose of semaglutide was 1 mg/week).<sup>5</sup></p>
<p style="text-align: justify; ">“This was an exciting study
that was published recently in the New England Journal of Medicine and it was
the first time we had compared tirzepatide with a GLP-1 agonist (semaglutide) in people with T2D.”</p></div><div class="pasted-from-word-wrapper">
<p style="text-align: justify; "><b>Figure 1 shows the design of the SURPASS-2 study <sup>1,4</sup></b></p></div><div contenteditable="false" data-width="980" style="left:0%;width:980px;" class="image-and-caption-wrapper clearfix hocalwire-draggable float-none"><img src="https://medicaldialogues.in/h-upload/2025/11/18/309294-1-s.webp" draggable="true" class="hocalwire-draggable float-none" data-float-none="true" data-uid="23690j3tObOgo1uheBrJPCgMiqtvdfRm4mM4e2814960" data-watermark="false" style="width: 100%; float: none;" info-selector="#info_item_1763462816139"><div class="inside_editor_caption image_caption hocalwire-draggable float-none" id="info_item_1763462816139"></div></div><div class="pasted-from-word-wrapper"></div><div class="pasted-from-word-wrapper">
<p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px; ">*Patients with T2D who had
inadequate glycemic control on stable doses of metformin alone to receive
once-weekly SC tirzepatide 5 mg, 10 mg, 15
mg, or once-weekly SC semaglutide 1 mg (1:1:1:1 ratio), all in combination with
metformin ≥1500 mg/day.</span></p><span style="font-size: 12px;">
</span><p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px;">†Stable doses of metformin
≥1500 mg/day for at least 3 months prior to Visit 1 and during the
screening/lead-in period.</span></p><span style="font-size: 12px;">
</span><p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px;">‡All tirzepatide doses were
double-blinded HbA1c = glycated hemoglobin; SC = subcutaneous; T2D = type 2
diabetes.</span></p>
<p style="text-align: justify; ">The objective of the
SURPASS-2 study was to demonstrate that tirzepatide used at a dose of 10mg or
15 mg once weekly was noninferior to semaglutide 1 mg once weekly, the highest
licensed dose available for the management of T2D at the time of SURPASS-2.<sup>4</sup></p>
<p style="text-align: justify; ">The primary endpoint of
SURPASS-2 was change in HbA1c from baseline to 40 weeks.<sup>4</sup></p>
<p style="text-align: justify; "><b>Key secondary endpoints
included<sup>4</sup>:</b></p>
<ul><li style="text-align: justify; ">Noninferiority of
tirzepatide 5 mg once weekly to semaglutide 1 mg once weekly for glycemic
control at 40 weeks.</li><li style="text-align: justify; ">Mean change from
baseline in HbA1c.</li><li style="text-align: justify; ">Superiority of
tirzepatide 5 mg, 10 mg and/or 15 mg once weekly to semaglutide 1 mg once
weekly at 40 weeks for:</li><li style="text-align: justify; ">Mean change from
baseline in body weight.</li><li style="text-align: justify; ">Mean change from
baseline in HbA1c.</li><li style="text-align: justify; ">Proportion of
patients with HbA1c target values of <7.0%.</li><li style="text-align: justify; ">Superiority of
tirzepatide 10 mg and/or 15 mg once weekly to semaglutide for the proportion of patients with HbA1c target values of <5.7% at 40 weeks<b>.</b></li></ul>
<p style="text-align: justify; "><b>Who was in SURPASS-2?</b></p>
<p style="text-align: justify; ">The SURPASS-2 study included
a total of 1878 patients with T2D who were receiving a background of metformin
therapy, with an HbA1c of ≥7.0% to ≤10.5%, and were randomized to one of the
four treatment arms.<sup>4</sup> At baseline, the mean age of patients was
56.6years, with a mean HbA1c of 8.3%, characteristic of such trials in patients
with T2D, a mean diabetes duration of 8.6 years, and a mean body mass index
(BMI) of 34 kg/m2 (Table 1).</p></div><div contenteditable="false" data-width="100%" style="left:NaN%;width:100%px;" class="image-and-caption-wrapper clearfix hocalwire-draggable float-none"><img src="https://medicaldialogues.in/h-upload/2025/11/18/309295-2-s.webp" draggable="true" class="hocalwire-draggable float-none" data-float-none="true" data-uid="23690xgblwDaIUVd0qZDsQanfRG7CI0EDewJ82956082" data-watermark="false" style="width: 100%; float: none;" info-selector="#info_item_1763462957334"><div class="inside_editor_caption image_caption hocalwire-draggable float-none" id="info_item_1763462957334"></div></div><div class="pasted-from-word-wrapper"><p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px; ">Note: data are mean ± SD
unless otherwise specified; mITT population.</span></p></div><div class="pasted-from-word-wrapper"><span style="font-size: 12px;">
</span><p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px;">BMI = body mass index; FSG =
fasting serum glucose; HbA1c = glycated hemoglobin; mITT = modified
intent-to-treat;</span></p><span style="font-size: 12px;">
</span><p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px;">SD = standard deviation.</span></p>
<p style="text-align: justify; "><b>Patient disposition</b></p>
<p style="text-align: justify; ">Of the 471 patients
randomized to tirzepatide 5 mg once weekly, 431 (91.5%) completed the study still
receiving the study drug, with corresponding figures for the 10 mg and 15 mg once-weekly
arms of 411/469 (87.6%) and 408/470 (86.8%), respectively, and 428/469 (91.3%)
for the semaglutide arm.</p>
<p style="text-align: justify; "><b>Primary endpoint: change
in HbA1c</b></p>
<p style="text-align: justify; ">Tirzepatide was associated
with greater change from baseline at 40 weeks in HbA1c than semaglutide, with
decreases of 2.1%, 2.4% and 2.5%, for tirzepatide 5 mg, 10 mg and 15 mg once
weekly, respectively, compared with 1.9% for semaglutide 1 mg once weekly all
(p<0,001; Figure 2).</p></div><div contenteditable="false" data-width="100%" style="left:NaN%;width:100%px;" class="image-and-caption-wrapper clearfix hocalwire-draggable float-none"><img src="https://medicaldialogues.in/h-upload/2025/11/18/309296-3-s.webp" draggable="true" class="hocalwire-draggable float-none" data-float-none="true" data-uid="23690uJSSgXLnjEvNrJqKUTH3OQCVnhtDuIx33018114" data-watermark="false" style="width: 100%; float: none;" info-selector="#info_item_1763463019198"><div class="inside_editor_caption image_caption hocalwire-draggable float-none" id="info_item_1763463019198"></div></div><div class="pasted-from-word-wrapper"><p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px;">*P<0.001 vs. semaglutide 1
mg for superiority, adjusted for multiplicity. Efficacy estimand. MMRM
analysis, mITT population (efficacy analysis set). Data presented are LS mean.</span></p></div><div class="pasted-from-word-wrapper"><span style="font-size: 12px;">
</span><p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px;">Tirzepatide vs. semaglutide 1
mg at 40 weeks.</span></p><span style="font-size: 12px;">
</span><p style="text-align: justify;line-height: 20px!important; "><span style="font-size: 12px;">HbA1c=glycated hemoglobin;
ETD=estimated treatment</span></p><span style="font-size: 12px;">
</span><p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px;">difference; LS=least squares;
mITT=modified intent-to-treat;</span></p><span style="font-size: 12px;">
</span><p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px;">MMRM=mixed model for repeated
measures.</span></p>
<p style="text-align: justify; "><b>All three doses of
tirzepatide showed a significantly greater reduction in HbA1c than semaglutide.<sup>4</sup></b></p>
<p style="text-align: justify; ">Moreover, the reductions in
HbA1c with tirzepatide were seen as early as Week 4 and then continued through
to Week 40 (Figure 3).</p></div><div contenteditable="false" data-width="100%" style="width:100%" class="image-and-caption-wrapper clearfix hocalwire-draggable float-none"><img src="https://medicaldialogues.in/h-upload/2025/11/18/309297-4-s.webp" draggable="true" class="hocalwire-draggable float-none" data-float-none="true" data-uid="23690OdRuBPsqCRH1dkCGGSvd0ziRq1pJO8O43088332" data-watermark="false" style="width: 100%;" info-selector="#info_item_1763463089385"><div class="inside_editor_caption image_caption hocalwire-draggable float-none" id="info_item_1763463089385"></div></div><div class="pasted-from-word-wrapper"><p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px;">P<0.001 for all tirzepatide
doses vs. semaglutide, adjusted for multiplicity. Triangles indicate the times
at which the maintenance doses of tirzepatide (5 mg, 10 mg, or 15 mg) and
semaglutide 1 mg were achieved. Efficacy estimand. MMRM analysis, mITT
population (efficacy analysis set). Data presented are LS mean. Tirzepatide vs.
semaglutide 1 mg at 40 weeks. HbA1c=glycated hemoglobin; LS=least squares;
mITT=modified intent-to-treat; MMRM=mixed model for repeated measures.</span></p></div><div class="pasted-from-word-wrapper">
<p style="text-align: justify; "><b>HbA1c goals</b></p>
<p style="text-align: justify; ">For the secondary endpoint of
proportion of patients meeting HbA1c goals, for the goal of an HbA1c of <7%,
all treatment arms, including semaglutide, had a high percentage of patients achieving
this goal, at 81% for semaglutide 1 mg once weekly and 86%-92% for tirzepatide.
However, for an HbA1c goal of <5.7%, only 20% of patients receiving
semaglutide 1 mg once weekly achieved this goal compared with 51% of patients
receiving tirzepatide 15 mg once weekly. (Figure 4a and Figure 4b).</p>
<p style="text-align: justify; ">Moreover, looking at 7-point
self-monitored blood glucose, all of the arms showed a downward shift, but
tirzepatide treatment was associated with greater reductions in daily mean
glucose, pre-meal daily mean glucose, and 2-hour post-meal glucose compared
with semaglutide.</p></div><div contenteditable="false" data-width="100%" style="left:NaN%;width:100%;" class="image-and-caption-wrapper clearfix hocalwire-draggable float-none"><img src="https://medicaldialogues.in/h-upload/2025/11/18/309298-5-s.webp" draggable="true" class="hocalwire-draggable float-none" data-float-none="true" data-uid="23690qF71RixRMkvkMuT5gDrQrgTcQ6nsOpb33147818" data-watermark="false" style="width: 100%; float: none;" info-selector="#info_item_1763463148824"><div class="inside_editor_caption image_caption hocalwire-draggable float-none" id="info_item_1763463148824"></div></div><div class="pasted-from-word-wrapper"><p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px;">*P<0.05 vs. semaglutide 1
mg for superiority, adjusted for multiplicity. †P<0.001 for superiority vs.
semaglutide 1 mg, adjusted for multiplicity.</span><sup><span style="font-size: 12px;">1§</span></sup><span style="font-size: 12px;">P<0.001 compared to
semaglutide 1 mg, not adjusted for multiplicity. </span><sup><span style="font-size: 12px;">II</span></sup><span style="font-size: 12px;">Normoglycemia is
defined by an HbA1c <5.7%. Efficacy estimand: estimated means, logistic
regression, mITT population (efficacy analysis set). Tirzepatide vs.
semaglutide 1 mg at 40 weeks.</span></p></div><div class="pasted-from-word-wrapper"><span style="font-size: 12px;">
</span><p style="text-align: justify;line-height: 20px!important; "><span style="font-size: 12px;">HbA1c=glycated hemoglobin;
mITT=modified intent-to-treat.</span></p>
<p style="text-align: justify; "><b>Superior mean weight
reduction</b></p>
<p style="text-align: justify; ">In addition to the superior
glycemic outcomes, tirzepatide was also shown to be associated with superior
mean weight reductions over semaglutide at Week 40, with tirzepatide 15 mg delivering
double the weight reduction of semaglutide 1 mg, at 12.4 kg, equating to around
a 13% weight-loss, compared with 6.2 kg (6.7%). (Figure 5)</p>
<p style="text-align: justify; ">Importantly, these
significant weight reductions from baseline over 40 weeks with tirzepatide were
observed as early as Week 4, and there was no plateau over the course of the
study. (figure 6)</p>
<p style="text-align: justify; ">The SURPASS-2 study also
looked at the proportions of patients reaching weight loss targets of at least
5%, 10% and 15%. </p>
<p style="text-align: justify; ">A weight loss of 5% would be
considered a really important outcome in a weight-loss trial, which this was
not; it is a Phase III glycemic control trial.</p>
<p style="text-align: justify; ">Yet in this trial, 58% of
patients receiving semaglutide 1 mg once weekly achieved a weight loss of 5%,
and 86% of those receiving the highest dose of tirzepatide achieved a weight
loss of 5%. When looking at weight loss, 9% of patients achieved 15% weight
loss with semaglutide 1 mg once weekly compared with 40% of those receiving the
15 mg once-weekly dose of tirzepatide.</p>
<p style="text-align: justify; ">Plotting reduction in BMI
shows that while there were reductions with semaglutide, there were relatively
greater, dose-dependent reductions seen with tirzepatide, and again we see
greater reductions in waist circumference, seeing around a 10 cm reduction in
waist circumference with tirzepatide 15 mg once weekly.</p></div><div contenteditable="false" data-width="100%" style="left:NaN%;width:100%px;" class="image-and-caption-wrapper clearfix hocalwire-draggable float-none"><img src="https://medicaldialogues.in/h-upload/2025/11/18/309299-6-s.webp" draggable="true" class="hocalwire-draggable float-none" data-float-none="true" data-uid="23690PXwrEh0ustb2o7UxcmiaOOPjUho9XlNO3223685" data-watermark="false" style="width: 100%; float: none;" info-selector="#info_item_1763463224891"><div class="inside_editor_caption image_caption hocalwire-draggable float-none" id="info_item_1763463224891"></div></div><div class="pasted-from-word-wrapper"><p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px;">†P<0.001 vs. semaglutide 1
mg for superiority, adjusted for multiplicity. ‡Percentage change from mean
weight at baseline.</span><span style="font-size: 12px;">Percentage of weight loss was
an approximate calculation of the LS mean for change from baseline divided by
the mean baseline value. Efficacy estimand. MMRM analysis, mITT population (efficacy
analysis set). Data presented are LS mean. Tirzepatide vs. semaglutide 1 mg at
40 weeks. Tirzepatide is not indicated for weight management. In clinical
trials, weight change was a secondary endpoint.</span><sup><span style="font-size: 12px;">1</span></sup><span style="font-size: 12px;"> LS=least squares;
mITT=modified intent-to-treat; MMRM=mixed model for repeated measures.</span></p></div><div contenteditable="false" data-width="100%" style="left:NaN%;width:100%px;" class="image-and-caption-wrapper clearfix hocalwire-draggable float-none"><img src="https://medicaldialogues.in/h-upload/2025/11/18/309300-7-s.webp" draggable="true" class="hocalwire-draggable float-none" data-float-none="true" data-uid="23690Q0eOpiC1TX2SaUb2MdXHVjC9M86Uc5UV3311762" data-watermark="false" style="width: 100%; float: none;" info-selector="#info_item_1763463312844"><div class="inside_editor_caption image_caption hocalwire-draggable float-none" id="info_item_1763463312844"></div></div><div class="pasted-from-word-wrapper"><p style="text-align: justify; line-height: 20px!important;margin-bottom: 0px!important;"><span style="font-size: 12px;">*In clinical trials, weight change was a secondary
endpoint</span><sup><span style="font-size: 12px;">.1</span></sup><span style="font-size: 12px;"> Triangles indicate the times at which the maintenance
doses of tirzepatide (5 mg, 10 mg, or 15 mg) and semaglutide 1 mg were
achieved. Efficacy estimand. MMRM analysis, mITT population (efficacy analysis
set). Data presented are LS mean. Tirzepatide vs. semaglutide 1 mg at 40 weeks.
LS=least squares; mITT=modified intent-to-treat; MMRM=mixed model for repeated
measures.</span></p></div><div class="pasted-from-word-wrapper">
<p style="text-align: justify; "><b>Beyond weight and glucose</b></p>
<p style="text-align: justify; ">It is important to look at
markers beyond weight and glucose. Regarding lipid profiles in patients
receiving tirzepatide or semaglutide in the SURPASS-2 trial, there were
reductions in triglycerides that were greater with tirzepatide than
semaglutide, as well as improvements in high-density lipoprotein cholesterol
and significant reductions in very low-density lipoprotein cholesterol.</p>
<p style="text-align: justify; "><b>Tolerability</b></p>
<p style="text-align: justify; ">There were increases seen in
gastrointestinal adverse events across all study arms with these incretin-based therapies, but
there were no notable differences between tirzepatide and semaglutide. Overall,
for gastrointestinal adverse effects, this figure was around 40% for
tirzepatide 5 mg, 46.1% and 44.9% for tirzepatide 10 mg and 15 mg once weekly, respectively,
compared with 41.2% for semaglutide 1 mg once weekly (Table 2).</p>
<p style="text-align: justify; ">Specifically, in terms of the
patterns of nausea, vomiting and diarrhea, these increased across all arms at
times of titration and tended to reduce over time, and most events were mild to
moderate.</p></div><div contenteditable="false" data-width="100%" style="left:NaN%;width:100%px;" class="image-and-caption-wrapper clearfix hocalwire-draggable float-none"><img src="https://medicaldialogues.in/h-upload/2025/11/18/309302-8-s.webp" draggable="true" class="hocalwire-draggable float-none" data-float-none="true" data-uid="23690JVZI3ZxhhygbID5NrR9dCM16yDrzHdyL3380726" data-watermark="false" style="width: 100%; float: none;" info-selector="#info_item_1763463381704"><div class="inside_editor_caption image_caption hocalwire-draggable float-none" id="info_item_1763463381704"></div></div><div class="pasted-from-word-wrapper"><p style="text-align: justify;line-height: 20px!important; "><span style="font-size: 12px;">mITT population. No clinically
relevant changes in mean calcitonin levels were observed, and no cases of
medullary thyroid cancer were reported. *This patient had a hypoglycemic event
that was not considered by the investigator to be severe, but it was reported
as a serious adverse event. Clinically significant hypoglycemia (BG <3.0
mmol/L [<54 mg/dL] or severe hypoglycemia [requiring the assistance of
another person]) occurred in 10–14% (0.14 to 0.16 events/patient year) of
patients when tirzepatide was added to
sulphonylurea and in 14–19% (0.43 to 0.64 events/patient year) of patients when
tirzepatide was added to basal insulin. The rate of clinically significant
hypoglycemia when tirzepatide was used as monotherapy or when added to other
oral antidiabetic medicinal products was up to 0.04 events/patient year. In
Phase 3 clinical studies,10 (0.2%) patients reported 12
episodes of severe hypoglycemia. Of these 10 patients, 5 (0.1%) were on a
background of insulin glargine or sulphonylurea who reported one episode each.</span></p></div><div class="pasted-from-word-wrapper"><span style="font-size: 12px;">
</span><p style="text-align: justify; "><span style="font-size: 12px;">AE = adverse event; BG = blood
glucose; GI = gastrointestinal; mITT = modified intent-to-treat.</span></p>
<p style="text-align: justify; "><b>Hypoglycemia</b></p>
<p style="text-align: justify; ">Rates of hypoglycemia in this
trial were low, and there were very few episodes of severe hypoglycemia.
Looking at adverse events of special interest, these were low and did not appear to be different
between semaglutide and tirzepatide (Table 2).</p>
<p style="text-align: justify; "><b>Blood pressure and heart
rate</b></p>
<p style="text-align: justify; ">There were reductions in both
systolic and diastolic blood pressure in the SURPASS-2 trial and an increase in heart
rate, which were similar with tirzepatide and semaglutide.</p>
<p style="text-align: justify; "><b>Conclusions</b></p>
<p style="text-align: justify; ">In the SURPASS-2 trial in
people with T2D inadequately controlled on metformin monotherapy, once-weekly
tirzepatide, a dual GIP/GLP-1 receptor agonist, demonstrated<sup>4</sup>:</p>
<ul><li style="text-align: justify; ">Superior and
clinically meaningful improvements in glycemic control.</li><li style="text-align: justify; ">Significant
reduction in body weight.</li><li style="text-align: justify; ">Achievements of
HbA1c reflecting almost normoglycemia (<5.7%) in up to 51% of participants.</li><li style="text-align: justify; ">Low risk of
hypoglycemia (blood glucose <54 mg/dL) or severe hypoglycemia.</li></ul>
<p style="text-align: justify; margin-bottom: 10px!important;"><b><span style="font-size: 12px;">References</span></b></p><span style="font-size: 12px;">
</span><p style="text-align: justify; font-size: 14px;
line-height: 20px;
margin-bottom: 0px !important;"><span style="font-size: 12px;">1. Tirzepatide India
Prescribing Information | Updated March 2025</span></p><span style="font-size: 12px;">
</span><p style="text-align: justify; font-size: 14px;
line-height: 20px;
margin-bottom: 0px !important;"><span style="font-size: 12px;">2. Nauck MA, Quast DR, Wefers
J, et al. GLP-1 receptor agonists in the treatment of type 2 diabetes -
state-of-the-art. Mol Metab. 2021;46:101102.</span></p><span style="font-size: 12px;">
</span><p style="text-align: justify; font-size: 14px;
line-height: 20px;
margin-bottom: 0px !important;"><span style="font-size: 12px;">3. Christensen M, Vedtofte L,
Holst JJ, et al. Glucose-dependent insulinotropic polypeptide: a bifunctional glucose-dependent
regulator of glucagon and insulin secretion in humans. Diabetes. 2011;60(12):3103-9.</span></p><span style="font-size: 12px;">
</span><p style="text-align: justify; font-size: 14px;
line-height: 20px;
margin-bottom: 0px !important;"><span style="font-size: 12px;">4. Frías JP, Davies MJ,
Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients
with type 2 diabetes. N Engl J Med. 2021;385(6):503-15.</span></p><span style="font-size: 12px;">
</span><p style="text-align: justify; font-size: 14px;
line-height: 20px;
margin-bottom: 0px !important;"><span style="font-size: 12px;">5.European Medicines Agency.
Ozempic. Summary of Product Characteristics 2018 [updated February 2022].
Available from: https://www.ema.europa.eu/documents/productinformation/ozempic-epar-
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