EVP, CFO & CAO at DexCom
Thank you, Kevin. As a reminder, unless otherwise noted, the financial metrics presented today will be discussed on a non-GAAP basis. Reconciliations to GAAP can be found in today's earnings release as well as on our IR website.
In line with our January pre-announcement, we reported worldwide revenue of $698 million for the fourth quarter compared to $569 million for the fourth quarter of 2020, representing growth of 23% on both a reported and constant currency basis and 20% on an organic basis.
The organic revenue excludes non-CGM revenue that we generated in the fourth quarter following our acquisition of our distributor in Australia and New Zealand. U.S. revenue totaled $517 million in the fourth quarter compared to $451 million in the fourth quarter of 2020, representing growth of 15%.
Unit volume growth, which is a general representation for the growth of our user base, remained in the high 30% range compared to the fourth quarter of 2020, and we continue to see the strength in our strategic shift to the pharmacy channel. Our teams continue to work very hard to broaden our prescriber base and take advantage of the significant reimbursement access that we have driven in the past 2 years in both the U.S. and international markets.
The uptick in COVID cases has created some challenges for us in the fourth quarter and into the early first quarter, but it is a credit to the resilience of our field team and the strength of the category that global new customers remain near record levels in the fourth quarter.
Our international business executed very well in the fourth quarter, with revenue growing 54%, totaling $181 million. Excluding non-CGM revenue that resulted from our 2021 distributor acquisition, international growth was 41% in the fourth quarter. The international result reflected broad-based strength, including record results in all of our direct markets.
This growth continues to validate the strategic moves that we made over the course of 2021, most notably the progress that we made to broaden access to our technology through advocacy, flexibility gained from operating efficiencies and a differentiated product portfolio. We look forward to extending this momentum now as we progress into 2022.
Our fourth quarter gross profit was $472.6 million or 67.7% of revenue compared to 70.2% of revenue in the fourth quarter of 2020. The fourth quarter gross margin was slightly above our expectations as certain costs related to the G7 scale-up and commercial preparation remain in our R&D costs until we receive CE Mark. We made excellent progress to drive efficiencies across our product design, procurement, manufacturing and logistics functions leading to a full year 2021 gross margin that finished 360 basis points above our original 2021 guidance.
Operating expenses were $373.6 million for Q4 2021 compared to $294.7 million in Q4 2020. The increase in operating expenses as a percentage of revenue relative to the fourth quarter of 2020 was primarily a result of development and operational costs incurred in preparation for the launch of G7 as well as investments to support our global commercialization efforts.
Operating income was $99 million in the fourth quarter of 2021 compared to $104.4 million in the same quarter of 2020. As a reminder, when we provided the outlook for 2021, we determined it was in the best interest to make investments in the business continue to fuel CGM growth and awareness.
As we wrap the year, we are proud to report that we outpaced our initial 2021 operating margin guidance by more than 200 basis points, all of which came despite significant investments to solidify our software advantages, advance the G7 clinical, regulatory and manufacturing programs, significantly expand our global sales force presence and significant efforts to build brand awareness. And we are committed to driving further leverage in the years to come as we strike the right balance between investing to maximize our growth opportunity and turning that opportunity into cash flow generation for the business and our stakeholders.
Adjusted EBITDA was $154.5 million or 22.1% of revenue for the fourth quarter compared to $159.2 million or 28% of revenue for the fourth quarter of 2020. Net income for the fourth quarter was $69 million or $0.68 per share. As many of you also saw in our press release and our GAAP reconciliations, we also recognized an $87 million expense associated with contingent milestone under the 2018 collaboration and license agreement with Verily Life Sciences. Terms of our amended contract with Verily are available in the SEC filings that were originally published in November 2018 and updated in November 2021.
We closed the quarter with greater than $2.7 billion in cash and cash equivalents. We have demonstrated the ability to generate positive cash flow. And going forward, we remain in a very flexible position to continue to advance strategic initiatives and opportunities. Most notably, we will continue our development of our manufacturing facility in Malaysia as we expect to have that facility validated for production by the end of 2022.
Turning to 2022 guidance. As we stated last month, we anticipate full year total revenues of $2.82 billion to $2.94 billion, representing growth of 15% to 20%. Given the success of our strategic transition to the pharmacy channel over the past 3 years, we anticipate that 2022 will be the final year where we see a significant shift of our existing base from the durable medical equipment channel to pharmacy.
With this ongoing shift as well as the majority of our new customers now coming through the pharmacy channel in the U.S., our expectations for customer growth in 2022 are again higher than our revenue growth rate, continuing to reflect the large end markets we serve and the growing demand for DexCom CGM worldwide. We have several scenarios built in conjunction with our plan G7 launches. And factoring in the respective regulatory approvals and competitive environment, we will provide updates as the year progresses.
Turning to margins. We are establishing the following guidance for 2022. We expect gross profit margins of approximately 65% for the year, in line with the expectation that we established for our 2025 long-range plan. The slight step back relative to our 2021 results is primarily related to the launch of our G7 system during the year as we begin production at lower volumes and gradually scale in conjunction with our launches.
Despite that step back in gross margin, we expect to offset that impact completely with approximately 400 basis points of operating expense leverage. We anticipate our operating margins of 2022 of approximately 16%. This factors in the ongoing investments that are driving significant returns for DexCom and setting us up for sustainable growth, including our DTC marketing efforts and investments in our product portfolio pipeline. We are making these investments with the discipline throughout the organization, driving towards the margin expansion that we've established in our long-range plan.
Finally, we expect adjusted EBITDA margins of approximately 25% in 2022.
With that, I will turn the call back to Kevin.